Cannabinoid receptor antagonists/inverse agonists useful for treating obesity

ABSTRACT

The present invention provides novel pyrazoles that are useful as cannabinoid receptor antagonists and pharmaceutical compositions thereof and methods of using the same for treating obesity, diabetes, and/or cardiometabolic disorders.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority benefit under 35 U.S.C. §119(e)of U.S. Provisional Patent Application Ser. No. 60/781,485 filed Mar.10, 2006. The disclosure this application is incorporated herein byreference.

FIELD OF THE INVENTION

The present invention provides cannabinoid receptor antagonists/inverseagonists and pharmaceutical compositions thereof and methods of usingthe same for treating obesity, diabetes, and/or cardiometabolicdisorders. More particularly, the present invention relates to a novelmethod for treating obesity, diabetes, and/or cardiometabolic disordersusing a pyrazole.

BACKGROUND OF THE INVENTION

Obesity is associated with an increase in the overall amount of adiposetissue (i.e., body fat), especially adipose tissue localized in theabdominal area. Obesity has reached epidemic proportions in the UnitedStates. The prevalence of obesity has steadily increased over the yearsamong all racial and ethnic groups. The most recent data from theCenters for Disease Control and Prevention, and the National Center forHealth Statistics report 66% of the adult population overweight (BMI,25.0-29.9), 31% obese (BMI, 30-39.9), and 5% extremely obese (BMI,≦40.0). Among children aged 6 through 19 years, 32% were overweight and17% were obese. This translates to 124 million Americans medicallyoverweight, and 44 million of these deemed obese. Obesity is responsiblefor more than 300,000 deaths annually, and will soon overtake tobaccousage as the primary cause of preventable death in the United States.Obesity is a chronic disease that contributes directly to numerousdangerous co-morbidities, including type 2 diabetes, cardiovasculardisease, inflammatory diseases, premature aging, and some forms ofcancer. Type 2 diabetes, a serious and life-threatening disorder withgrowing prevalence in both adult and childhood populations, is currentlythe 7^(th) leading cause of death in the United States. Since more than80% of patients with type 2 diabetes are overweight, obesity is thegreatest risk factor for developing type 2 diabetes. Increasing clinicalevidence indicates that the best way to control type 2 diabetes is toreduce weight.

The most popular over-the counter drugs for the treatment of obesity,phenylpropanolamine and ephedrine, and the most popular prescriptiondrug, fenfluramine, were removed from the marketplace as a result ofsafety concerns. Drugs currently approved for the long-term treatment ofobesity fall into two categories: (a) CNS appetite suppressants such assibutramine and (b) gut lipase inhibitors such as orlistat. CNS appetitesuppressants reduce eating behavior through activation of the ‘satietycenter’ in the brain and/or by inhibition of the ‘hunger center’ in thebrain. Gut lipase inhibitors reduce the absorption of dietary fat fromthe gastrointestinal (GI) tract. Although sibutramine and orlistat workthrough very different mechanisms, they share in common the same overallgoal of reducing body weight secondary to reducing the amount ofcalories that reach the systemic circulation. Unfortunately, theseindirect therapies produce only a modest initial weight loss(approximately 5% compared to placebo) that is usually not maintained.After one or two years of treatment, most patients return to or exceedtheir starting weight. In addition, most approved anti-obesitytherapeutics produce undesirable and often dangerous side effects thatcan complicate treatment and interfere with a patient's quality of life.

The lack of therapeutic effectiveness, coupled with the spiralingobesity epidemic, positions the ‘treatment of obesity’ as one of thelargest and most urgent unmet medical needs. There is, therefore, a realand continuing need for the development of improved medications thattreat or prevent obesity.

The endocanabinoid system, comprised of the canabinoid receptors (CB1and CB2) and their endogenous ligands (e.g., anandamide, 2-AG), plays aprominent role in the control of food intake and energy metabolism. CB1receptors are widely expressed in the brain, including cortex,hippocampus, amygdala, pituitary and hypothalamus. CB1 receptors havealso been identified in numerous peripheral organs and tissues,including thyroid gland, adrenal gland, reproductive organs, adiposetissue, liver, muscle, and gastrointestinal tract. CB2 receptors arelocalized almost exclusively in immune and blood cells [EndocrineReviews 2006, 27, 73].

The plant-derived cannabinoid agonist Δ⁹-tetrahydrocannabinol (Δ⁹-THC),the main psychoactive component of marijuana, binds to both CB1 and CB2receptors. Δ⁹-THC is widely reported to increase appetite and foodintake (hyperphagia) in humans and in animals. This hyperphagic effectis largely blocked by pretreatment with selective CB1 receptorantagonists/inverse agonists [e.g., rimonabant (SR141716A, Acomplia®)],strongly supporting the belief that CB1 receptor activation mediates thehyperphagic effect of Δ⁹-THC, [Endocrine Reviews 2006, 27, 73].

In humans, rimonabant produces a clinically meaningful weight loss inobese patients. Patients also experience improvements in associatedcardiometabolic risk factors, including a decrease in fasting insulinlevels and a decrease in triglyceride levels. Rimonabant also producesgreater reductions in abdominal fat deposits, which are a known riskfactor for diabetes and heart disease [Science 2006, 311, 323]. Takentogether, these improvements in adiposity and cardiometabolic riskfactors produce an overall decrease in the prevalence of the metabolicsyndrome [Lancet 2005, 365, 1389 and NEJM2005, 353, 2121].

The beneficial effects of rimonabant on cardiometabolic risk factorssuch as high blood pressure, insulin resistance and elevated levels ofblood lipids cannot be explained by diet and weight loss alone. Forexample, in patients receiving 20 mg of rimonabant, only approximately50% of the beneficial effects on triglycerides, fasting insulin, andinsulin resistance can be accounted for by weight loss. These resultssuggest a direct pharmacological effect of CB1 antagonists on glucoseand lipid metabolism, in addition to indirect effects on metabolismsecondary to hypophagia-mediated weight loss [Science 2006, 311, 323 andJAMA 2006, 311, 323].

The CB1 receptor is one of the most abundant and widely distributed Gprotein-coupled receptors in the mammalian brain. It is believed thatthe appetite-suppressant properties of CB1 antagonists are mediatedthrough an interaction with CB1 receptors in the hypothalamus(regulation of food intake), and in the mesolimbic region (rewardingproperties of food). However, CB1 receptors are far more broadlydistributed in brain (e.g., neocortex, hippocampus, thalamus,cerebellum, and pituitary), and while interacting with targeted CB1receptors in hypothalamus and mesolimbic regions, CB1 antagonists haveready access to non-targeted CB1 receptors that have little if any rolein appetite control. Binding to non-targeted receptors can often lead tounwanted side effects of CNS drugs [Endocrine Reviews 2006, 27: 73]. TheCB1 antagonist/inverse agonist rimonabant produces psychiatric andnervous system side effects. These include depressed mood, anxiety,irritability, insomnia, dizziness, and headache. These side effects aredose-related and are most pronounced at the most efficaciousweight-reducing dose of rimonabant (JAMA 2006, 311, 323). The occurrenceof therapeutic efficacy (appetite suppression) and side effects over thesame dose range strongly suggest that both effects are mediated throughconcurrent antagonism of CB1 receptors in both ‘targeted’ and‘non-targeted’ brain regions. Brain-penetrant CB1 antagonists/inverseagonists do not selectively target CB1 receptors in efficacy brainregions, while ignoring CB1 receptors in side effect brain regions.

The beneficial effects of the CB1 antagonist rimonabant on body weight,adiposity, and cardiometabolic risk factors such as high blood pressure,insulin resistance and elevated levels of blood lipids cannot beexplained by weight loss derived from CNS-mediated appetite suppressionalone [JAMA 2006, 311, 323]. Approximately 50% of the non-CNS benefit islikely derived from an interaction with CB1 receptors in peripheraltissues known to play an active role in metabolism. These includeadipose tissue, liver, muscle, and gastrointestinal tract.

In view of the above, it is highly desirable to find effective andhighly selective CB1 receptor antagonists/inverse agonists with limitedor no CNS adverse side effects, including mood disorders. Particularly,it is desirable to find compounds that preferentially target CB1receptors in peripheral tissues (e.g., adipose tissue, liver, muscle,and gastrointestinal tract), while sparing CB1 receptors in brain. Inthis way, peripherally-mediated beneficial effects of CB1antagonists/inverse agonists should be maintained, whereas CNS sideeffects should be reduced or eliminated. This should provide a novelopportunity to develop safer agents for the prevention or treatment ofobesity, diabetes, and cardiometabolic diseases (e.g., hypertension anddyslipidemias).

SUMMARY OF THE INVENTION

Accordingly, in an aspect, the present invention provides novelpyrazoles or pharmaceutically acceptable salts thereof that are CB1receptor antagonists/inverse agonists.

In another aspect, the present invention provides novel pharmaceuticalcompositions, comprising: a pharmaceutically acceptable carrier and atherapeutically effective amount of at least one of the compounds of thepresent invention or a pharmaceutically acceptable salt form thereof.

In another aspect, the present invention provides novel methods fortreating obesity, diabetes, and/or cardiometabolic disorders (e.g.,hypertension, dyslipidemias, high blood pressure, and insulinresistance), comprising: administering to a mammal in need of suchtreatment a therapeutically effective amount of at least one of thecompounds of the present invention or a pharmaceutically acceptable saltform thereof.

In another aspect, the present invention provides processes forpreparing novel compounds.

In another aspect, the present invention provides novel compounds orpharmaceutically acceptable salts for use in therapy.

In another aspect, the present invention provides the use of novelcompounds for the manufacture of a medicament for the treatment ofobesity, diabetes, and/or cardiometabolic disorders.

These and other objects, which will become apparent during the followingdetailed description, have been achieved by the inventors' discoverythat the presently claimed compounds or pharmaceutically acceptable saltforms thereof are expected to be effective CB1 receptorantagonists/inverse agonists.

DETAILED DESCRIPTION OF THE INVENTION

All references cited herein are hereby incorporated in their entiretyherein by reference.

The present invention is based on the finding that a CB1 receptorantagonist/inverse agonist has beneficial effects on body weight,adiposity, and cardiometabolic risk factors such as high blood pressure,insulin resistance and eleveated levels of blood lipids that cannot beexplained by weight loss derived from CNS-mediated appetite suppressionalone and that this effect is mediated, at least in part, throughinteraction at peripheral receptors. To this end, the present inventionprovides compounds that are designed to preferentially target CB1receptors in peripheral tissues (e.g., adipose tissue, liver, muscle,and gastrointestinal tract), while sparing CB1 receptors in brain.Peripherally-mediated beneficial effects of CB1 antagonists/inverseagonists should be maintained, whereas CNS side effects should bereduced or eliminated.

The compounds of the present invention have been designed to havereduced CNS exposure by virtue of their inability or limited ability topenetrate the blood-brain barrier (BBB) or by their participation inactive transport systems, thus reducing centrally mediated side-effects,a potential problem with many anti-obesity agents. It is expected thatthe peripherally restricted compounds of the present invention will haveno or very limited CNS effects. Thus, their peripherally mediated CB1antaonistic properties should provide therapeutic agents with greatersafety.

Moreover, if the maximum dosage of a drug used in the treatment ofobesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension,dyslipidemias, high blood pressure, and insulin resistance) is limitedas a result of CNS side effects (e.g., seizures, depression, anxiety,movement disorders, and hyperactivity), incorporation of a peripherallyrestricting group in such a drug would lower the brain concentration ofthe drug relative to the concentration in the systemic circulation,thereby affording the opportunity to increase the dosage employed totreat the peripheral disorder. The increased dosage may provide greatertherapeutic efficacy, as well as a more rapid onset of therapeuticaction.

[1] In an embodiment, the present invention provides novel compound AAor a stereoisomer or pharmaceutically acceptable salt thereof:

wherein:

X, Y, X′, and Y′ are independently selected from H, halogen, CF₃, NO₂,C₁₋₆ alkyl, C₁₋₆ alkoxy, and phenyl;

V is H or C₁₋₆ alkyl;

R″ is selected from H, C₁₋₆ alkyl, (CH₂)₀₋₆ aryl, and (CH₂)₀₋₆heteroaryl

R′ is selected from H, C₁₋₆ alkyl, and a 5-7 membered cyclic amine thatis unsaturated, partially saturated, or fully saturated and issubstituted with 0-4 groups selected from CF₃, NO₂, C₁₋₆ alkyl, benzyl,phenyl, OH, halogen, and C₁₋₆ alkoxy;

ring R′ is attached via its nitrogen atom to the amide nitrogen of AA;and

at least one of X, Y, X′, Y′, V, R′, or R″ is suitably modified orreplaced by a group capable of reducing or limiting the CNS (brain)levels of compound AA.

[2] In an embodiment, the present invention provides novel compounds offormula I or a stereoisomer or pharmaceutically acceptable salt thereof:

wherein:

X and Y are independently selected from H, halogen, C₁₋₆ alkyl, NO₂,CF₃, NR₂, OR, CO₂R, (CH₂)_(n)CO₂R, O(CH₂)_(n)CO₂R, OCH₂CH═CHCO₂R,CH₂O(CH₂)_(n)CO₂R, CH₂OCH₂CH═CHCO₂R,O(CH₂)_(n)PO(OR)₂,CH₂O(CH₂)_(n)PO(OR)₂, NR¹(CH₂)_(n)CO₂R,NR^(a)(CH₂)_(n)PO(OR)₂, NR^(a)CH₂CH═CHCO₂R, NR^(a)SO₂CH₃,NR^(a)CO(CH₂)_(n)CO₂R, O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄(CH₂)_(n)CO₂R,CH₂O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄(CH₂)_(n)CONH₂, CH₂O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄-tetrazole, CH₂O(CH₂)_(n)C₆H₄-tetrazole,O(CH₂)_(n)C₆H₄(CH₂)_(n),-tetrazole, NR^(a)(CH₂)_(n)C₆H₄CO₂R,CH₂NR^(a)(CH₂)_(n)C₆H₄CO₂R, NR^(a)(CH₂)_(n)C₆H₄CONH₂,CH₂NR^(a)(CH₂)_(n)C₆H₄CONH₂, NR^(a)(CH₂)_(n)C₆H₄-tetrazole,CH₂NR^(a)(CH₂)_(n)C₆H₄-tetrazole, —CN, (CH₂)_(m)C(NH)NH₂, CONR₂,(CH₂)_(n)CONR₂, O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONH₂,NR^(a)(CH₂)_(n)CONR₂, OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂,NR^(a)CH₂CH═CHCONR₂,-tetrazole, O(CH₂CH₂O)_(p)R, NR^(a)(CH₂CH₂O)_(p)R,and SO₂NR^(a)CH₃;

X′ and Y′ are independently selected from H, halogen, C₁₋₆ alkyl, NO₂,CF₃, NR₂, OR, CO₂R, (CH₂)_(n)CO₂R, O(CH₂)_(n)CO₂R, OCH₂CH═CHCO₂R,CH₂O(CH₂)_(n)CO₂R, CH₂OCH₂CH═CHCO₂R,O(CH₂)_(n)PO(OR)₂,CH₂O(CH₂)_(n),PO(OR)₂, NR^(a)(CH₂)_(n)CO₂R,NR^(a)(CH₂)_(n)PO(OR)₂, NR^(a)CH₂CH═CHCO₂R, NR^(a)SO₂CH₃,N^(a)CO(CH₂)_(n)CO₂R, O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄(CH₂)_(n)CO₂R,CH₂O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄(CH₂)_(n)CONH₂, CH₂O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄-tetrazole, CH₂O(CH₂)_(n)C₆H₄-tetrazole,O(CH₂)_(n)C₆H₄(CH₂)_(n)-tetrazole, NR^(a)(CH₂)_(n)C₆H₄CO₂R,CH₂NR^(a)(CH₂)_(n)C₆H₄CO₂R, NR^(a)(CH₂)_(n)C₆H₄CONH₂,CH₂NR^(a)(CH₂)_(n)C₆H₄CONH₂, NR_(a)(CH₂)_(n)C₆H₄-tetrazole,CH₂NR^(a)(CH₂)_(n)C₆H₄-tetrazole, —CN, (CH₂)_(m)C(NH)NH₂, CONR₂,(CH₂)_(n)CONR₂, O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONH₂,NR^(a)(CH₂)_(n)CONR₂, OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂,NR^(a)CH₂CH═CHCONR₂,-tetrazole, O(CH₂CH₂O)_(p)R, NR^(a)(CH₂CH₂O)_(p)R,and SO₂NR^(a)CH₃;

A is selected from H, C₁₋₆ alkyl, (CH₂)_(m)-C₃₋₆-cycloalkyl,(CH₂)_(m)-heteroaryl, and (CH₂)_(m)-aryl, wherein each aryl andheteroaryl is substituted with 0-1 groups selected from CF₃, halogen,C₁₄ alkyl, —CN, CONR₂, NO₂, NR₂, and OR;

R′ is selected from H, C₁₋₆ alkyl, CH(A)-(CH₂)_(m)CO₂R,CH(A)-(CH₂)_(m)CONH₂, CH(A)-(CH₂)_(m)C(NH)NH₂,(CH₂)_(m)-phenyl-(CH₂)_(m)CO₂R, (CH₂)_(m)-pyridyl-(CH₂)_(m)CO₂R,(CH₂)_(m)-phenyl-(CH₂)_(m)CONH₂, (CH₂)_(m)-pyridyl-(CH₂)_(m)CONH₂,(CH₂)_(m)-phenyl-(CH₂)_(m)C(NH)NH₂, (CH₂)_(m)-pyridyl-(CH₂)_(m)(CN)NH₂,(CH₂)_(m)-phenyl-(CH₂)_(m)-tetrazole, and(CH₂)_(m)-pyridyl-(CH₂)_(m)-tetrazole;

alternatively, R′ is

R″ is is selected from H, C₁₋₆ alkyl, (CH₂)₀₋₆ aryl, and (CH₂)₀₋₆heteroaryl;

Z is selected from H, C₁₋₆ alkyl, aryl, NR₂, OR, —CN, (CH₂)_(m)C(NH)NH₂,CO₂R, (CH₂)_(n)CO₂R, O(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CO₂R, NR^(a)CH(A)CO₂R,CH₂NR^(a)CH(A)CO₂R, NR^(a)(CH₂)_(n)CO₂R CH₂NR^(a)(CH₂)_(n)CO₂ROCH₂CH═CHCO₂R, CH₂OCH₂CH═CHCO₂R O(CH₂)_(n)PO(OR)₂, CH₂O(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)C₆H₄CO₂R, CH₂O(CH₂)_(n)C₆H₄CO₂R, CONR₂, (CH₂)_(n)CONR₂,O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONR₂, OCH₂CH═CHCONR₂CH₂OCH₂CH═CHCONR₂,CH₂NR^(a)(CH₂)_(n)tetrazole, CH₂O(CH₂)_(n)tetrazole, and(CH₂)_(m)tetrazole;

Q is selected from N, CH, and CQ′;

Q′ is selected from H, CO₂R, (CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CO₂R,CH₂OCH₂CH═CHCO₂R, CH₂O(CH₂)_(n)PO(OR)₂, CONR₂, (CH₂)_(n)CONR₂,CH₂O(CH₂)_(n)CONR₂, CH₂OCH₂CH═CHCONR₂, and (CH₂)_(m)tetrazole;

V is selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, CF₃, aryl, —CN,(CH₂)_(m)C(NH)NH₂, (CH₂)_(m)Co₂R, (CH₂)_(m)CONR₂, (CH₂)_(m)-tetrazole,(CH₂)_(m)CONR^(a)CH(A)-(CH₂)_(m)CO₂R,(CH₂)_(m)CONR^(a)(CH₂)_(m)-phenyl-(CH₂)_(m)CO₂R,(CH₂)_(m)CONR^(a)(CH₂)_(m)-phenyl-(CH₂)_(m)-tetrazole,CH₂O(CH₂)_(n)CO₂R, CH₂NR^(a)(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CONH₂,CH₂NR^(a)(CH₂)_(n)CONH₂, and CH₂O(CH₂)_(n)tetrazole;

R is independently selected from H, C₁₋₆ alkyl;

R^(a) is independently selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, andC₂₋₆ alkynyl

m is selected from 0, 1, 2, 3, and 4;

n is selected from 1, 2, 3, and 4; and,

p is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12;

provided that at least one of the following is satisfied:

-   -   (a) at least one of X, Y, X′, and Y′ is other than H, halogen,        C₁₋₆ alkyl, NO₂, —CN, CF₃, OR, and phenyl;    -   (b) R′ is selected from CH(A)-(CH₂)_(m)CO₂R,        CH(A)-(CH₂)_(m)CONH₂, CH(A)-(CH₂)_(m)C(NH)NH₂,        (CH₂)_(m)-phenyl-(CH₂)_(m)CO₂R, (CH₂)_(m)-pyridyl-(CH₂)_(m)CO₂R,        (CH₂)_(m)-phenyl-(CH₂)_(m)CONH₂,        (CH₂)_(m)-pyridyl-(CH₂)_(m)CONH₂,        (CH₂)_(m)-phenyl-(CH₂)_(m)C(NH)NH₂,        (CH₂)_(m)-pyridyl-(CH₂)_(m)(CN)NH₂,        (CH₂)_(m)-phenyl-(CH₂)_(m)-tetrazole, and        (CH₂)_(m)-pyridyl-(CH₂)_(m)-tetrazole;    -   (c) Z is present and is other than H, C₁₋₆ alkyl, aryl, NR₂, and        OR;    -   (d) Q is present and is CQ′ where Q′ is other than H; and/or    -   (e) V is other than H, —CN, CF₃, C₂₋₆ alkenyl, aryl, and C₁₋₆        alkyl.

[3] In another embodiment, the present invention provides novelcompounds of formula II or a stereoisomer or pharmaceutically acceptablesalt thereof:

[4] In another embodiment, the present invention provides novelcompounds of formula IIa or a stereoisomer or pharmaceuticallyacceptable salt thereof:

[5] In another embodiment, the present invention provides novelcompounds of formula II, wherein:

X and Y are independently selected from H, halogen, C₁₋₄ alkyl, CF₃,—CN, NO₂, NR₂, and OR;

X′ and Y′ are independently selected from H, halogen, C₁₋₄ alkyl, CF₃,—CN, NO₂, NR₂, and OR;

Z is selected from (CH₂)_(m)C(NH)NH₂, (CH₂)_(m)CO₂R, O(CH₂)_(n)CO₂R,CH₂O(CH₂)_(n)CO₂R, NR^(a)CH(A)CO₂R, CH₂NR^(a)CH(A)CO₂R,NR^(a)(CH₂)_(n)CO₂R CH₂NR^(a)(CH₂)_(n)CO₂R OCH₂CH═CHCO₂R,CH₂OCH₂CH═CHCO₂R, O(CH₂)_(n)PO(OR)₂, CH₂O(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)C₆H₄CO₂R, CH₂O(CH₂)_(n)C₆H₄CO₂R, (CH₂)_(m)CONR₂,O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONR₂, OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂,CH₂NR^(a)(CH₂)_(n)tetrazole, CH₂O(CH₂)_(n)tetrazole, and(CH₂)_(m)tetrazole;

Q is selected from N and CH;

V is selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, CF₃, aryl, and —CN;

R is selected from H, C₁₋₄ alkyl, and C₂₋₄ alkenyl; and,

n is selected from 1 and 2.

[6] In another embodiment, the present invention provides novelcompounds of formula II, wherein:

X and Y are independently selected from H, halogen, C₁₋₆ alkyl, NO₂,CF₃, NR₂, OR, —CN, (CH₂)_(m)C(NH)NH₂, (CH₂)_(m)CO₂R, O(CH₂)_(n)CO₂R,OCH₂CH═CHCO₂R, CH₂O(CH₂)_(n)CO₂R, CH₂OCH₂CH═CHCO₂R,O(CH₂)_(n)PO(OR)₂,CH₂O(CH₂)_(n)PO(OR)₂, NR^(a)(CH₂)_(n)CO₂R,NR^(a)(CH₂)_(n)PO(OR)₂, NR^(a)CH₂CH═CHCO₂R, NR^(a)SO₂CH₃,NR^(a)CO(CH₂)_(n)CO₂R, O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄(CH₂)_(n)CO₂R,CH₂O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄(CH₂)_(n)CONH₂, O(CH₂)_(n)C₆H₄-tetrazole,CH₂O(CH₂)_(n)C₆H₄CONH₂, CH₂O(CH₂)_(n)C₆H₄-tetrazole,O(CH₂)_(n)C₆H₄(CH₂)_(n)-tetrazole, NR^(a)(CH₂)_(n)C₆H₄CO₂R,CH₂NR^(a)(CH₂)_(n)C₆H₄CO₂R, NR^(a)(CH₂)_(n)C₆H₄CONH₂,CH₂NR^(a)(CH₂)_(n)C₆H₄CONH₂, NR^(a)(CH₂)_(n)C₆H₄-tetrazole,CH₂NR^(a)(CH₂)_(n)C₆H₄-tetrazole, CONR₂, (CH₂)_(n)CONR₂,O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONH₂, NR^(a)(CH₂)_(n)CONR₂,OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂, NR^(a)CH₂CH═CHCONR₂,-tetrazole,O(CH₂CH₂O)_(p)R, NR^(a)(CH₂CH₂O)_(p)R, and SO₂NR^(a)CH₃;

provided that at least one of X and Y is other than H, halogen, C₁₋₆alkyl, —CN, NO₂, CF₃, and OR;

X′ and Y′ are independently selected from H, halogen, C₁₋₄ alkyl, —CN,NO₂, NR₂, and OR;

Z is selected from H, C₁₋₄ alkyl, and aryl;

Q is selected from N and CH;

V is selected from H, C₁₋₄ alkyl, and aryl;

R is selected from H, C₁₋₄ alkyl, and C₂₋₄ alkenyl; and,

n is selected from 1 and 2.

[7] In another embodiment, the present invention provides novelcompounds of formula II, wherein:

X and Y are independently selected from H, halogen, C₁₋₄ alkyl, —CN,NO₂, NR₂, and OR;

X′ and Y′ are independently selected from H, halogen, C₁₋₆ alkyl, —CN,NO₂, CF₃, NR₂, OR, CO₂R, (CH₂)_(n)CO₂R, (CH₂)_(m)C(NH)NH₂,O(CH₂)_(n)CO₂R, OCH₂CH═CHCO₂R, CH₂O(CH₂)_(n)CO₂R, CH₂OCH₂CH═CHCO₂R,O(CH₂)_(n)PO(OR)₂,CH₂O(CH₂)_(n)PO(OR₂, NR^(a)(CH₂)_(n)CO₂R,NR^(a)(CH₂)_(n)PO(OR)₂, NR^(a)CH₂CH═CHCO₂R, NR^(a)SO₂CH₃,NR^(a)CO(CH₂)_(n)CO₂R, O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄(CH₂)_(n) CO₂R,CH₂O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄(CH₂,O(CH₂)_(n)C₆H₄-tetrazole, CH₂O(CH₂)_(n)C₆H₄CONH₂,CH₂O(CH₂)_(n)C₆H₄-tetrazole, O(CH₂)_(n)C₆H₄(CH₂)_(n)-tetrazole,NR^(a)(CH₂)_(n)C₆H₄CO₂R, CH₂NR^(a)(CH₂)_(n)C₆H₄CO₂R,NR^(a)(CH₂)_(n)C₆H₄CONH₂, CH₂NR^(a)(CH₂)_(n)C₆H₄CONH₂,NR^(a)(CH₂)_(n)C₆H₄-tetrazole, CH₂NR^(a)(CH₂)_(n)C₆H₄-tetrazole, CONR₂,(CH₂)_(n)CONR₂, O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONH₂,NR^(a)(CH₂)_(n)CONR₂, OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂,NR^(a)CH₂CH═CHCONR₂,-tetrazole, O(CH₂CH₂O)_(p)R, NR^(a)(CH₂CH₂O)_(p)R,and SO₂NR^(a)CH₃;

provided that at least one of X′ and Y′ is other than halogen, C₁₋₄alkyl, —CN, NO₂, and OR;

Z is selected from H, C₁₋₄ alkyl, and aryl;

Q is selected from N and CH;

V is selected from H, C₁₋₄ alkyl, and aryl;

R is selected from H, C₁₋₄ alkyl, and C₂₋₄ alkenyl;

n is selected from 1 and 2; and,

p is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12.

[8] In another embodiment, the present invention provides novelcompounds of formula II, wherein:

X and Y are independently selected from H, CF₃, halogen, C₁₋₄ alkyl,—CN, NO₂, NR₂, and OR;

X′ and Y′ are independently selected from H, CF₃, halogen, C₁₋₄ alkyl,—CN, NO₂, NR₂, and OR;

Z is selected from H, C₁₋₄ alkyl, and aryl;

Q is selected from N and CH;

V is selected from (CH₂)_(m)CO₂R, (CH₂)_(m)CONR₂, (CH₂)_(m)C(NH)NH₂,(CH₂)_(m)-tetrazole, (CH₂)_(m)CONR^(a)CH(A)-(CH₂)_(m)CO₂R,(CH₂)_(m)CONR^(a)(CH₂)_(m)-phenyl-(CH₂)_(m)CO₂R,(CH₂)_(m)CONR^(a)(CH₂)_(m)-phenyl-(CH₂)_(m)-tetrazole,CH₂O(CH₂)_(n)CO₂R, CH₂NR^(a)(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CONH₂,CH₂NR^(a)(CH₂)_(n)CONH₂, and CH₂O(CH₂)_(n)tetrazole;

A is selected from H, C₁₋₄ alkyl, and (CH₂)_(m)-aryl, wherein each arylis optionally substituted with 0-1 groups selected from CF₃, halogen,C₁₋₄ alkyl, —CN, CONR₂, NO₂, NR₂, and OR;

R is selected from H, C₁₋₄ alkyl, and C₂₋₄ alkenyl;

m is selected from 0, 1, and 2; and,

n is selected from 1 and 2.

[9] In another embodiment, the present invention provides novelcompounds of formula I, wherein:

X and Y are independently selected from H, CF₃, halogen, C₁₋₄ alkyl,—CN, NO₂, NR₂, and OR;

X′ and Y′ are independently selected from H, CF₃, halogen, C₁₋₄ alkyl,—CN, NO₂, NR₂, and OR;

R′ is selected from CH(A)-(CH₂)_(m)CO₂R, CH(A)-(CH₂)_(m)CONH₂,CH(A)-(CH₂)_(m)C(NH)NH₂, (CH₂)_(m)-phenyl-(CH₂)_(m)CO₂R,(CH₂)_(m)-pyridyl-(CH₂)_(m)CO₂R, (CH₂)_(m)-phenyl-(CH₂)_(m)CONH₂,(CH₂)_(m)-pyridyl-(CH₂)_(m)CONH₂, (CH₂)_(m)-phenyl-(CH₂)_(m)C(NH)NH₂,(CH₂)_(m)-pyridyl-(CH₂)_(m)(CN)NH₂,(CH₂)_(m)-phenyl-(CH₂)_(m)-tetrazole, and(CH₂)_(m)-pyridyl-(CH₂)_(m)-tetrazole;

A is selected from H, C₁₋₆ alkyl, (CH₂)_(m)-C₃₋₆-cycloalkyl,(CH₂)_(m)-phenyl, (CH₂)_(m)-aryl, and (CH₂)_(m)-heteroaryl, wherein eacharyl, phenyl, and heteroaryl is optionally substituted with 0-1 groupsselected from CF₃, halogen, C₁₋₄ alkyl, —CN, CONR₂, NO₂, NR₂, and OR;

V is selected from H, C₁₋₄ alkyl, and aryl;

R is selected from H, C₁₋₄ alkyl; and,

m is selected from 0, 1, and 2.

In another embodiment, the present invention provides novelpharmaceutical compositions, comprising: a pharmaceutically acceptablecarrier and a therapeutically effective amount of a compound of thepresent invention or a pharmaceutically acceptable salt form thereof.

In another embodiment, the present invention provides a novel method fortreating a disease, comprising: administering to a patient in needthereof a therapeutically effective amount of a compound of the presentinvention or a pharmaceutically acceptable salt form thereof, whereinthe disease is selected from obesity, diabetes, cardiometabolicdisorders, and a combination thereof.

In another embodiment, the diabetes disorder is selected from Type 1diabetes, Type 2 diabetes, inadequate glucose tolerance, and insulinresistance.

In another embodiment, the cardiometabolic disorder is selected fromhypertension, dyslipidemias (e.g., undesirable blood lipid levels,elevated cholesterol levels, and lowered LDL levels), high bloodpressure, and insulin resistance.

In another embodiment, the present invention provides a novel method fortreating a co-morbidity of obesity, comprising: administering to apatient in need thereof a therapeutically effective amount of a compoundof the present invention or a pharmaceutically acceptable salt formthereof.

In another embodiment, the co-morbidity is selected from diabetes,Metabolic Syndrome, dementia, and heart disease.

In another embodiment, the co-morbidity is selected from hypertension;gallbladder disease; gastrointestinal disorders; menstrualirregularities; degenerative arthritis; venous statis ulcers; pulmonaryhypoventilation syndrome; sleep apnea; snoring; coronary artery disease;arterial sclerotic disease; pseudotumor cerebri; accident proneness;increased risks with surgeries; osteoarthritis; high cholesterol; and,increased incidence of malignancies of the ovaries, cervix, uterus,breasts, prostrate, and gallbladder.

In another embodiment, the present invention also provides a method ofpreventing or reversing the deposition of adipose tissue in a mammal bythe administration of a compound of the present invention. By preventingor reversing the deposition of adipose tissue, compound of the presentinvention are expected to reduce the incidence or severity of obesity,thereby reducing the incidence or severity of associated co-morbidities.

In another embodiment, the present invention provides a compound of thepresent invention for use in therapy.

In another embodiment, the present invention provides the use of thepresent invention for the manufacture of a medicament for the treatmentof obesity, diabetes, cardiometabolic disorders, and a combinationthereof.

The present invention may be embodied in other specific forms withoutdeparting from the spirit or essential attributes thereof. Thisinvention encompasses all combinations of aspects of the invention notedherein. It is understood that any and all embodiments of the presentinvention may be taken in conjunction with any other embodiment orembodiments to describe additional embodiments. It is also to beunderstood that each individual element of the embodiments is intendedto be taken individually as its own independent embodiment. Furthermore,any element of an embodiment is meant to be combined with any and allother elements from any embodiment to describe an additional embodiment.

The examples provided in the definitions present in this application arenon-inclusive unless otherwise stated. They include but are not limitedto the recited examples.

The compounds herein described may have asymmetric centers, geometriccenters (e.g., double bond), or both. All chiral, diastereomeric,racemic forms and all geometric isomeric forms of a structure areintended, unless the specific stereochemistry or isomeric form isspecifically indicated. Compounds of the present invention containing anasymmetrically substituted atom may be isolated in optically active orracemic forms. It is well known in the art how to prepare opticallyactive forms, such as by resolution of racemic forms, by synthesis fromoptically active starting materials, or through use of chiralauxiliaries. Geometric isomers of olefins, C═N double bonds, or othertypes of double bonds may be present in the compounds described herein,and all such stable isomers are included in the present invention.Specifically, cis and trans geometric isomers of the compounds of thepresent invention may also exist and may be isolated as a mixture ofisomers or as separated isomeric forms. All processes used to preparecompounds of the present invention and intermediates made therein areconsidered to be part of the present invention. All tautomers of shownor described compounds are also considered to be part of the presentinvention.

“Alkyl” includes both branched and straight-chain saturated aliphatichydrocarbon groups having the specified number of carbon atoms. C₁₋₆alkyl, for example, includes C₁, C₂, C₃, C₄, C₅, and C₆ alkyl groups.Examples of alkyl include methyl, ethyl, n-propyl, i-propyl, n-butyl,s-butyl, t-butyl, n-pentyl, and s-pentyl.

“Alkenyl” includes the specified number of hydrocarbon atoms in eitherstraight or branched configuration with one or more unsaturatedcarbon-carbon bonds that may occur in any stable point along the chain,such as ethenyl and propenyl. C₂₋₆ alkenyl includes C₂, C₃, C₄, C₅, andC₆ alkenyl groups.

“Alkynyl” includes the specified number of hydrocarbon atoms in eitherstraight or branched configuration with one or more triple carbon-carbonbonds that may occur in any stable point along the chain, such asethynyl and propynyl. C₂₋₆ Alkynyl includes C₂, C₃, C₄, C₅, and C₆alkynyl groups.

“Cycloalkyl” includes the specified number of hydrocarbon atoms in asaturated ring, such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, and cyclooctyl. C₃₋₈ cycloalkyl includes C₃,C₄, C₅, C₆, C₇, and C₈ cycloalkyl groups.

“Cyclic amine” is a hydrocarbon ring wherein one carbon atom of the ringhas been replaced by a nitrogen atom. The cyclic amine can beunsaturated, partially saturated, or fully saturated. The cyclic aminecan also be bicyclic, tricyclic, and polycyclic. Examples of cyclicamine include pyrrolidine and piperdine.

Halo” or “halogen” refers to fluoro, chloro, bromo, and iodo.

“Counterion” is used to represent a small, negatively charged species,such as chloride, bromide, hydroxide, acetate, and sulfate.

The group “C₆H₄” represents a phenylene.

“Aryl” refers to any stable 6, 7, 8, 9, 10, 11, 12, or 13 memberedmonocyclic, bicyclic, or tricyclic ring, wherein at least one ring, ifmore than one is present, is aromatic. Examples of aryl includefluorenyl, phenyl, naphthyl, indanyl, adamantyl, and tetrahydronaphthyl.

“Heteroaryl” refers to any stable 5, 6, 7, 8, 9, 10, 11, or 12 memberedmonocyclic, bicyclic, or tricyclic heterocyclic ring that is aromatic,and which consists of carbon atoms and 1, 2, 3, or 4 heteroatomsindependently selected from the group consisting of N, O, and S. If theheteroaryl group is bicyclic or tricyclic, then at least one of the twoor three rings must contain a heteroatom, though both or all three mayeach contain one or more heteroatoms. If the heteroaryl group isbicyclic or tricyclic, then only one of the rings must be aromatic. TheN group may be N, NH, or N-substituent, depending on the chosen ring andif substituents are recited. The nitrogen and sulfur heteroatoms mayoptionally be oxidized (e.g., S, S(O), S(O)₂, and N—O). The heteroarylring may be attached to its pendant group at any heteroatom or carbonatom that results in a stable structure. The heteroaryl rings describedherein may be substituted on carbon or on a nitrogen atom if theresulting compound is stable.

Examples of heteroaryl includes acridinyl, azocinyl, benzimidazolyl,benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl,benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl,benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl,4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl,decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolyl,1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl,isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl,isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl,oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl,phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathinyl, phenoxazinyl, phthalazinyl, pteridinyl, pyranyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole,pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, 2H-pyrrolyl, pyrrolyl,quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl,tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl,1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl,thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl,thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl.

“Mammal” covers warm blooded mammals that are typically under medicalcare (e.g., humans and domesticated animals). Examples of mammalsinclude feline, canine, equine, bovine, and human, as well as justhuman.

“Treating” or “treatment” covers the treatment of a disease-state in amammal, and includes: (a) preventing the disease-state from occurring ina mammal, in particular, when such mammal is predisposed to thedisease-state but has not yet been diagnosed as having it; (b)inhibiting the disease-state, i.e., arresting it development; and/or (c)relieving the disease-state, i.e., causing regression of the diseasestate until a desired endpoint is reached.

“Pharmaceutically acceptable salts” refer to derivatives of thedisclosed compounds wherein the parent compound is modified by makingacid or base salts thereof. Examples of pharmaceutically acceptablesalts include, but are not limited to, mineral or organic acid salts ofbasic residues such as amines; alkali or organic salts of acidicresidues such as carboxylic acids; and the like. The pharmaceuticallyacceptable salts include the conventional non-toxic salts or thequaternary ammonium salts of the parent compound formed, for example,from non-toxic inorganic or organic acids. For example, suchconventional non-toxic salts include, but are not limited to, thosederived from inorganic and organic acids selected from1,2-ethanedisulfonic, 2-acetoxybenzoic, 2-hydroxyethanesulfonic, acetic,ascorbic, benzenesulfonic, benzoic, bicarbonic, carbonic, citric,edetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic,gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic,hydrabamic, hydrobromic, hydrochloric, hydroiodide, hydroxymaleic,hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic,maleic, malic, mandelic, methanesulfonic, napsylic, nitric, oxalic,pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic,propionic, salicyclic, stearic, subacetic, succinic, sulfamic,sulfanilic, sulfuric, tannic, tartaric, and toluenesulfonic.

The pharmaceutically acceptable salts of the present invention can besynthesized from the parent compound that contains a basic or acidicmoiety by conventional chemical methods. Generally, such salts can beprepared by reacting the free acid or base forms of these compounds witha stoichiometric amount of the appropriate base or acid in water or inan organic solvent, or in a mixture of the two; generally, non-aqueousmedia like ether, ethyl acetate, ethanol, isopropanol, or acetonitrileare useful. Lists of suitable salts are found in Remington'sPharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, Pa.,1990, p 1445.

“Therapeutically effective amount” includes an amount of a compound ofthe present invention that is effective when administered alone or incombination to treat obesity or another indication listed herein.“Therapeutically effective amount” also includes an amount of thecombination of compounds claimed that is effective to treat the desiredindication. The combination of compounds can be a synergisticcombination. Synergy, as described, for example, by Chou and Talalay,Adv. Enzyme Regul. 1984, 22:27-55, occurs when the effect of thecompounds when administered in combination is greater than the additiveeffect of the compounds when administered alone as a single agent. Ingeneral, a synergistic effect is most clearly demonstrated atsub-optimal concentrations of the compounds. Synergy can be in terms oflower cytotoxicity, increased effect, or some other beneficial effect ofthe combination compared with the individual components.

Obesity is defined as having a body mass index (BMI) of 30 or above. Theindex is a measure of an individual's body weight relative to height.BMI is calculated by dividing body weight (in kilograms) by height (inmeters) squared. Normal and healthy body weight is defined as having aBMI between 20 and 24.9. Overweight is defined as having a BMI≧25.Obesity has reached epidemic proportions in the U.S., with 44 millionobese Americans, and an additional eighty million deemed medicallyoverweight.

Obesity is a disease characterized as a condition resulting from theexcess accumulation of adipose tissue, especially adipose tissuelocalized in the abdominal area. It is desirable to treat overweight orobese patients by reducing their amount of adipose tissue, and therebyreducing their overall body weight to within the normal range for theirsex and height. In this way, their risk for co-morbidities such asdiabetes and cardiovascular disease will be reduced. It is alsodesirable to prevent normal weight individuals from accumulatingadditional, excess adipose tissue, effectively maintaining their bodyweights at a BMI<25, and preventing the development of co-morbidities.It is also desirable to control obesity, effectively preventingoverweight and obese individuals from accumulating additional, excessadipose tissue, reducing the risk of further exacerbating theirco-morbidities.

Cannabinoid receptors are located in a number of peripheral (non-CNS)tissues, including thyroid gland, adrenal gland, reproductive organs,adipose tissue, liver, muscle, and gastrointestinal tract. Cannabinoidreceptor antagonists/inverse agonists being developed to treat obesityand smoking cessation, regardless of route of administration, enter theCNS from the systemic circulation. While present in the systemiccirculation, such drugs have access to peripheral tissues. One of skillin the art recognizes that cannabinoid receptor antagonists/inverseagonists intended to enter the CNS from the systemic circulation inorder to treat obesity and smoking cessation, also have access tocannabinoid receptors in peripheral tissues. Thus, a cannabinoidreceptor antagonist/inverse agonist useful for the present invention mayhave some access to the CNS from the systemic circulation.

Drugs enter the CNS from the systemic circulation by crossing theblood-brain barrier (BBB). The BBB is a highly specialized ‘gate-keeper’that protects the brain by preventing the entry of many potentiallyharmful substances into the CNS from the systemic circulation. Much isknown about the BBB, and of the physical-chemical properties requiredfor compounds transported across it.

Drugs that do not cross the BBB into the CNS or that are readilyeliminated through transport mechanisms [J Clin Invest. 97, 2517(1996)]are known in the literature and have low CNS activity due to theirinability to develop brain levels necessary for pharmacological action.The BBB has at least one mechanism to remove drugs prior to theiraccumulation in the CNS. P-Glycoproteins (P-gp) localized in plasmamembrane of the BBB can influence the brain penetration andpharmacological activity of many drugs through translocation acrossmembranes. The lack of accumulation into the brain by some drugs can beexplained by their active removal from the brain by P-gp residing in theBBB. For example, the typical opioid drug loperamide, clinically used asan antidiarrheal, is actively removed from the brain by P-gp, thusexplaining its lack of opiate-like CNS effects. Another example isdomperidone, a dopamine receptor blocker that participates in the P-gptransport [J Clin Invest. 97, 2517(1996)]. Whereas dopamine receptorblockers that cross the BBB can be used to treat schizophrenia, thereadily-eliminated domperidone can be used to prevent emesis, withoutthe likelihood of producing adverse CNS effects.

In addition to the above compounds, agents possessing structuralcharacteristics that retard or prevent BBB penetration or contribute toparticipation in active elimination processes have been identified invarious classes of therapeutics. These include antihistamines [DrugMetab. Dispos. 31, 312 (2003)], beta-adrenergic receptor antagonists(B-blockers) [Eur. J. Clin. Pharmacol. 28, Suppl: 21-3 (1985); Br. J.Clin. Pharmacol, 11 (6), 549-553 (1981)], non-nucleoside reversetranscriptase inhibitors (NNRTIs) [J. Pharm Sci., 88(10) 950-954(1999)], and opioid antagonists. This latter group has been tested inrelation to their activity in the GI tract. These peripherally selectiveopioid antagonists are described in various U.S. patents as being usefulin the treatment of non—CNS pathologies in mammals, in particular thoseof the GI tract [see U.S. Pat. No. 5,260,542; U.S. Pat. No. 5,434,171;U.S. Pat. No. 5,159,081; and U.S. Pat. No. 5,270,238].

Other types of non-brain penetrant compounds can be prepared through thecreation of a charge within the molecule. Thus, the addition of a methylgroup to the tertiary amine functionality of the drugs scopolamine oratropine, unlike the parent molecules, prevents their passage across theBBB through the presence of a positive charge. However, the newmolecules (methyl-scopolamine and methyl-atropine) retain their fullanticholinergic pharmacological properties. As such, these drugs canalso be used to treat peripheral diseases, without the concern ofadverse CNS effects. The quaternary ammonium compound methylnaltrexoneis also used for the prevention and/or treatment of opioid andnon-opioid induced side effects associated with opioid administration.

The discovery that the anti-obesity activity of cannabinoid receptorantagonists/inverse agonists may in part be mediated by a non-CNSmechanism could make it beneficial for the compounds of the presentinvention to be peripherally restricted, i.e., have an inability orlimited ability to cross the BBB, or be readily eliminated from thebrain through active transport systems. It may be desirable for thecompounds of the present invention to be peripherally restricted, whichin turn will result in no or very limited CNS effects. Compounds thatprovide peripherally mediated anti-obesity properties should result intherapeutic agents with greater safety. It can be desirable that thecompounds of the present invention, when administered in atherapeutically effective amount, have no or very limited CNS effects.It can also be desirable that the lack of CNS effects is a result of thecompounds of the present invention having minimal brain concentrationswhen administered in therapeutically effective amounts. In this context,minimal brain concentrations means levels that are too low to betherapeutically effective for the treatment of a CNS indication or toolow to cause significant or measurable deleterious or undesired sideeffects.

Rimonabant (Compound IIa when X═H; Y, X′, and Y′═Cl; V═CH₃; Z=H; Q=N;and n=2) is a drug that crosses the BBB and is indicated for thetreatment of obesity. In compound AA, one of R, R′, R″, X, X¹, V and Zis a group capable of reducing or limiting the CNS activity of compoundAA. This reduced or limited CNS activity occurs via at least one of R,R′, R″, X, X¹, V and Z being a group that either limits compound AA'sability to cross the BBB relative to that of rimonabant or enables it tobe actively removed from the brain at a rate greater than that ofrimonabant. Examples of the amount of compound AA present in the braincan include (a) from 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94,95, 96, 97, 98, 99, to 100% lower than rimonabant, (b) from 90, 91, 92,93, 94, 95, 96, 97, 98, 99, to 100% lower than rimonabant, and (c) from98, 99, to 100% lower than rimonabant, when administered at the samedosage.

The compounds of the present invention are expected to be cannabinoidreceptor antagonists or inverse agonists.

An inverse agonist is compound that not only blocks the action of theendogenous agonist at the receptor, but also exhibits its own activitywhich is usually the opposite of that shown by the agonist. Inverseagonists are also effective against certain types of receptors (e.g.certain histamine receptors/GABA receptors) which have intrinsicactivity without the interaction of a ligand upon them (also referred toas ‘constitutive activity’).

Most methods of treating obesity are dependent on a significantreduction in energy intake, either by a decrease in food intake (e.g.,sibutramine) or by inhibition of fat absorption (e.g., orlistat). In thepresent invention, adipose tissue may be reduced in the absence of asignificant reduction in food intake. The weight loss, as a result ofthe present invention, comes from the treatment with a compound of thepresent invention, largely independent of, though not totallydissociated from, appetite and food intake. It can be desirable thatadipose tissue loss occurs while food intake is maintained, increased or(a) about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, or 20% below the normal range of the subject prior to being treatedin accordance with the present invention (i.e., its pre-administrationlevel), (b) about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15%below its pre-administration level, (c) about 1, 2, 3, 4, 5, 6, 7, 8, 9,or 10% below its pre-administration level, or (d) about 1, 2, 3, 4, or5% below its pre-administration level.

In some cases, loss of adipose tissue can be accompanied by aconcomitant loss of lean muscle mass. This is particularly evident incancer patients who show a generalized wasting of body tissues,including adipose tissue and lean muscle mass. In the present invention,however, it can be desirable for body fat to be significantly reduced inthe absence of a significant reduction in lean body mass. Adipose tissueloss comes from treatment with a compound of the present invention,independent of a significant change in lean body mass. Thus, adiposetissue loss can occur while lean body mass is maintained, increased, or(a) is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30% belowthe normal range of the subject prior to being treated in accordancewith the present invention (i.e., its pre-administration level), (b) isno more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15%below pre-administration levels, (c) is no more than about 1, 2, 3, 4,5, 6, 7, 8, 9, or 10% below pre-administration levels, or (d) is no morethan about 1, 2, 3, 4, or 5% below pre-administration levels.

In some cases, loss of adipose tissue can be accompanied by aconcomitant loss of water mass. This is particularly evident with dietregimens that promote dehydration. In the present invention, it can bedesirable for body fat to be significantly reduced in the absence of asignificant reduction in water mass. In other words, adipose tissue losscomes from treatment with a compound of the present invention,independent of a significant change in water mass. It can be desirablethat adipose tissue loss occurs while water mass is maintained,increased, or (a) is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, or 30% below the normal range of the subject prior to being treatedin accordance with the present invention (i.e., its pre-administrationlevel), (b) is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, or 15% below pre-administration levels, (c) is no more thanabout 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% below pre-administration levels,or (d) is no more than about 1, 2, 3, 4, or 5% below pre-administrationlevels.

Sibutramine and orlistat are currently marketed for use in the treatmentof obesity. These two compounds achieve weight loss through entirelydifferent mechanisms. Sibutramine, a CNS appetite suppressant, inhibitsthe neuronal reuptake of serotonin and noradrenaline. Orlistat inhibitsgut lipase enzymes that are responsible for breaking down ingested fat.

Cannabinoid receptor antagonists/inverse agonists can promote weightloss through inhibition of peripheral cannabinoid receptors, a mechanismentirely different from appetite suppressants, gut lipase inhibitors,and other agents with similar indications (e.g., serotonin agonists,leptin, fatty acid synthase inhibitors, and monoamine oxidase (MAO)inhibitors). Co-administration of a cannabinoid receptorantagonist/inverse agonist together with one or more other agents thatare useful for treating the indications described above (e.g., obesity,diabetes, cardiometabolic disorders, and a combination thereof) isexpected to be beneficial, by producing, for example, either additive orsynergistic effects. Examples of additional agents include an appetitesuppressant, a lipase inhibitor, and a MAO inhibitor (e.g., MAO-B and acombination of MAO-A/B). Therefore, the present invention provides amethod of treating obesity, diabetes, and/or cardiometabolic disorders,comprising administering a therapeutically effective amount of acompound of the present invention and a second component effective fortreating the desired indication.

Examples of second components include anti-obesity agents, whichinclude, but are not limited to: 1) growth hormone secretagogues; 2)growth hormone secretagogue receptor agonists/antagonists; 3)melanocortin agonists; 4) Mc4r (melanocortin 4 receptor) agonists; 5).beta.-3 agonists; 7) 5HT2C (serotonin receptor 2C) agonists; 8) orexinantagonists; 9) melanin concentrating hormone antagonists; 10)melanin-concentrating hormone 1 receptor (MCH1R) antagonists; 11)melanin-concentrating hormone 2 receptor (MCH₂R) agonist/antagonists;12) galanin antagonists; 13) CCK agonists; 14) CCK-A (cholecystokinin-A)agonists; 16) corticotropin-releasing hormone agonists; 17) NPY 5antagonists; 18) NPY 1 antagonists; 19) histamine receptor-3 (H3)modulators; 20) histamine receptor-3 (H3) antagonists/inverse agonists;21)β-hydroxy steroid dehydrogenase-1 inhibitors (.beta.-HSD-1); 22) PDE(phosphodiesterase) inhibitors; 23) phosphodiesterase-3B (PDE3B)inhibitors; 24) NE (norepinephrine) transport inhibitors; 25)non-selective serotonin/norepinephrine transport inhibitors, such assibutramine, phentermine, or fenfluramine; 26) ghrelin antagonists; 28)leptin derivatives; 29) BRS3 (bombesin receptor subtype 3) agonists; 30)CNTF (Ciliary neurotrophic factors); 31) CNTF derivatives, such asaxokine (Regeneron); 32) monoamine reuptake inhibitors; 33) UCP-1(uncoupling protein-1), 2, or 3 activators; 34) thyroid hormone .beta.agonists; 35) FAS (fatty acid synthase) inhibitors; 37) DGAT2(diacylglycerol acyltransferase 2) inhibitors; 38) ACC2 (acetyl-CoAcarboxylase-2) inhibitors; 39) glucocorticoid antagonists; 40)acyl-estrogens; 41) lipase inhibitors, such as orlistat (Xenical®); 42)fatty acid transporter inhibitors; 43) dicarboxylate transporterinhibitors; 44) glucose transporter inhibitors; 45) phosphatetransporter inhibitors; 46) serotonin reuptake inhibitors; 47) Metformin(Glucophage®); 48) Topiramate (Topimax®); and/or 49) MAO inhibitors.

Examples of MAO inhibitors include Moclobemide; Brofaromine; BW A616U;Ro 41-1049; RS-2232; SR 95191; Harmaline; Harman; Amiflamine; BW1370U87; FLA 688; FLA 788; Bifemelane; Clorgyline; LY 51641; MDL 72,394;5-(4-Benzyloxyphenyl)-3-(2-cyanoethyl)-(3H)-1,3,4-oxadiazol-2-one;5-(4-Arylmethoxyphenyl)-2-(2-cyanoethyl)tetrazoles; Lazabemide; Ro16-6491; Almoxatone; XB308; RS-1636; RS-1653; NW-1015; SL 340026;.L-selegiline; Rasagiline; Pargyline; AGN 1135; MDL 72,974; MDL 72,145;MDL 72,638; LY 54761; MD 780236; MD 240931; Bifemelane; Toloxatone;Cimoxatone; Iproniazid; Phenelzine; Nialamide; Phenylhydrazine;1-Phenylcyclopropylamine; Isocarboxazid; and, Tranylcypromine.Additional examples of MAO inhibitors can be found in USPA 2007/0004683;U.S. application Ser. No. 11/445,044; USPA 2007/0015734; and U.S.application Ser. No. 11/424,274.

Examples of diabetes disorders include treating Type 1 diabetes, Type 2diabetes, inadequate glucose tolerance, and insulin resistance.

Examples of second components useful for treating diabetes include (a)insulin sensitizers including (i) PPAR-γ agonists such as the glitazones(e.g. troglitazone, pioglitazone, englitazone, MCC-555, rosiglitazone),and compounds disclosed in WO97/27857, 97/28115, 97/28137, and 97/27847;and (ii) biguanides such as metformin and phenformin; (b) insulin orinsulin mimetics; (c) sulfonylureas such as tolbutamide and glipizide,or related materials; (d) α-glucosidase inhibitors (e.g., acarbose); (e)cholesterol lowering agents such as (i) HMG-CoA reductase inhibitors(lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin,rivastatin, and other statins), (ii) sequestrants (e.g., cholestyramine,colestipol, and dialkylaminoalkyl derivatives of a cross-linkeddextran), (iii) nicotinyl alcohol, nicotinic acid or a salt thereof,(iv) PPAR-α agonists (e.g., fenofibric acid derivatives includinggemfibrozil, clofibrate, fenofibrate, and bezafibrate), (v) inhibitorsof cholesterol absorption (e.g., β-sitosterol) and acyl CoA:cholesterolacyltransferase inhibitors (e.g., melinamide), and (vi) probucol; (f)PPAR-α/γ agonists; (g) antiobesity compounds (described previously); (h)ileal bile acid transporter inhibitors; and (i) insulin receptoractivators.

The compounds of the present invention are expected to be CB1 receptorinhibitors/inverse agonists and are expected to be useful for treatingdiseases mediated by the CB₁ receptor. The compounds of the present areexpected to possess an affinity in vitro for the central and/orperipheral cannabinoid receptors under the experimental conditionsdescribed by Devane et al., Molecular Pharmacology, 1988, 34, 605-613.The compounds according to the invention are also expected to possess anaffinity for the cannabinoid receptors present on preparations ofelectrically stimulated isolated organs. These tests can be performed onguinea-pig ileum and on mouse vas deferens according to Roselt et al.,Acta Physiologica Scandinavia 1975, 94, 142-144, and according toNicolau et al., Arch. Int. Pharmacodyn, 1978, 236, 131-136.

CB1 receptor affinities can be determined using membrane preparations ofChinese hamster ovary (CHO) cells in which the human cannabinoid CB1receptor is stably transfected (Biochem J. 1991, 279, 129-134) inconjunction with [3H]CP-55,940 as radioligand. After incubation of afreshly prepared cell membrane preparation with the [3H]-radioligand,with or without addition of test compound, separation of bound and freeligand is performed by filtration over glass fiber filters.Radioactivity on the filter is measured by liquid scintillationcounting. The IC₅₀ values can be determined from at least threeindependent measurements.

In the present invention, the compound(s) of the present invention canbe administered in any convenient manner (e.g., enterally orparenterally). Examples of methods of administration include orally andtransdermally. One skilled in this art is aware that the routes ofadministering the compounds of the present invention may varysignificantly. In addition to other oral administrations, sustainedrelease compositions may be favored. Other acceptable routes may includeinjections (e.g., intravenous, intramuscular, subcutaneous, andintraperitoneal); subdermal implants; and, buccal, sublingual, topical,rectal, vaginal, and intranasal administrations. Bioerodible,non-bioerodible, biodegradable, and non-biodegradable systems ofadministration may also be used. Examples of oral formulations includetablets, coated tablets, hard and soft gelatin capsules, solutions,emulsions, and suspensions.

If a solid composition in the form of tablets is prepared, the mainactive ingredient can be mixed with a pharmaceutical vehicle, examplesof which include silica, starch, lactose, magnesium stearate, and talc.The tablets can be coated with sucrose or another appropriate substanceor they can be treated so as to have a sustained or delayed activity andso as to release a predetermined amount of active ingredientcontinuously. Gelatin capsules can be obtained by mixing the activeingredient with a diluent and incorporating the resulting mixture intosoft or hard gelatin capsules. A syrup or elixir can contain the activeingredient in conjunction with a sweetener, which is preferablycalorie-free, an antiseptic (e.g., methylparaben and/or propylparaben),a flavoring, and an appropriate color. Water-dispersible powders orgranules can contain the active ingredient mixed with dispersants orwetting agents or with suspending agents such as polyvinylpyrrolidone,as well as with sweeteners or taste correctors. Rectal administrationcan be effected using suppositories, which are prepared with bindersmelting at the rectal temperature (e.g., cocoa butter and/orpolyethylene glycols). Parenteral administration can be effected usingaqueous suspensions, isotonic saline solutions, or injectable sterilesolutions, which contain pharmacologically compatible dispersants and/orwetting agents (e.g., propylene glycol and/or polyethylene glycol). Theactive ingredient can also be formulated as microcapsules ormicrospheres, optionally with one or more carriers or additives. Theactive ingredient can also be presented in the form of a complex with acyclodextrin, for example α-, β-, or γ-cyclodextrin,2-hydroxypropyl-β-cyclodextrin, and/or methyl-β-cyclodextrin.

The dose of the compound of the present invention administered dailywill vary on an individual basis and to some extent may be determined bythe severity of the disease being treated (e.g., obesity, diabetes, andcardiometabolic disorders). The dose of the compound of the presentinvention will also vary depending on the compound administered.Examples of dosages of compounds of the present invention include fromabout 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2,0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 76, 80, 85, 90, 95, to 100mg/kg of mammal body weight. The compound can be administered in asingle dose or in a number of smaller doses over a period of time. Thelength of time during which the compound is administered varies on anindividual basis, and can continue until the desired results areachieved (i.e., reduction of body fat, or prevention of a gain in bodyfat). Therapy could, therefore, last from 1 day to weeks, months, oreven years depending upon the subject being treated, the desiredresults, and how quickly the subject responds to treatment in accordancewith the present invention.

A possible example of a tablet of the present invention is as follows.

Ingredient mg/Tablet Active ingredient 100 Powdered lactose 95 Whitecorn starch 35 Polyvinylpyrrolidone 8 Na carboxymethylstarch 10Magnesium stearate 2 Tablet weight 250

A possible example of a capsule of the present invention is as follows.

Ingredient mg/Tablet Active ingredient 50 Crystalline lactose 60Microcrystalline cellulose 34 Talc 5 Magnesium stearate 1 Capsule fillweight 150

In the above capsule, the active ingredient has a suitable particlesize. The crystalline lactose and the microcrystalline cellulose arehomogeneously mixed with one another, sieved, and thereafter the talcand magnesium stearate are admixed. The final mixture is filled intohard gelatin capsules of suitable size.

A possible example of an injection solution of the present invention isas follows.

Ingredient mg/Tablet Active substance  1.0 mg 1 N HCl 20.0 μl aceticacid  0.5 mg NaCl  8.0 mg Phenol 10.0 mg 1 N NaOH q.s. ad pH 5 H₂O q.s.ad 1 mLSynthesis

The compounds of the present invention can be prepared in a number ofways known to one skilled in the art of organic synthesis (e.g., see EP0,658,546, J Med Chem 2002, 45, 2708). The compounds of the presentinvention can be synthesized using the methods described below, togetherwith synthetic methods known in the art of synthetic organic chemistry,or by variations thereon as appreciated by those skilled in the art.Preferred methods include, but are not limited to, those describedbelow. The reactions are performed in a solvent appropriate to thereagents and materials employed and suitable for the transformationsbeing effected. It will be understood by those skilled in the art oforganic synthesis that the functionality present on the molecule shouldbe consistent with the transformations proposed. This will sometimesrequire a judgment to modify the order of the synthetic steps or toselect one particular process scheme over another in order to obtain adesired compound of the invention. It will also be recognized thatanother major consideration in the planning of any synthetic route inthis field is the judicious choice of the protecting group used forprotection of the reactive functional groups present in the compoundsdescribed in this invention. An authoritative account describing themany alternatives to the trained practitioner is Greene and Wuts(Protective Groups In Organic Synthesis, Wiley and Sons, 1991).

Scheme 1 shows how the condensation of a propiophenone with diethyloxalate in the presence of a base such as lithium hexamethydilsilazideshould afford, after acidification with hydrochloric acid solution, thediketoester (step a). Heating this ester with an aryl hydrazine in asolvent such as ethanol should produce the pyrazole ester along with theuncyclized imine (step b). These materials may be separated due to theirsolubility differences, or heated together in ethanolic hydroxidesolution to cause further conversion of the imine to the pyrazole alongwith concomitant saponification of the ester to the carboxylic acid(step c). Subsequent conversion of the carboxylic acid to the acidchloride using thionyl chloride followed by treatment with ethylN-aminonipecotate should afford the hydrazide ester (step d). Hydrolysisof the ester with lithium hydroxide and acidification with dilutehydrochloric acid solution should yield the hydrazide carboxylic acid(step e). Treatment of this acid with thionyl chloride followed byammonia should afford the carboxamide (step f).

Alternatively, the acid chloride generated from the product of step ccan be treated with N-amino-2-pyrrolidine methanol O—CH₂CO₂Et derivativeto produce the hydrazide ester (step g). Subsequent hydrolysis of thisester with aqueous base should afford the carboxylic acid (step h).

Scheme 2 describes how the conversion of the carboxylic acid from Scheme1 to its acid chloride using thionyl chloride or oxalyl chloride indichloroethane at elevated temperatures followed by treatment with ethyl4-aminocyclohexane carboxylate in the presence of triethyl amine shouldafford the amide ester (step a). Hydrolysis of the ester with lithiumhydroxide and acidification with dilute hydrochloric acid solutionshould yield the amide carboxylic acid (step b). When this acid isfurther treated with Boc anhydride (Boc₂O) in THF in the presence ofpyridine, followed by a solution of ammonia in THF at 0 degrees toambient temperature, the carboxamido compound will be produced (step c).

Alternatively, the acid chloride generated from the acid of Scheme 1 canbe treated with 2-amino-cyclopentylmethanol O—CH₂CO₂Et derivative toproduce the amide ester (step c). Subsequent hydrolysis of this esterwith aqueous base should afford the carboxylic acid (step d).

Scheme 3 depicts the conversion of the carboxylic acid from Scheme 1 toits acid chloride using thionyl chloride or oxalyl chloride indichloroethane at ambient to elevated temperatures followed by treatmentwith an amine such as alanine ethyl ester (A=methyl, n=0) in thepresence of triethylamine to afford the amide ester (step a). Hydrolysisof the ester with lithium hydroxide in aqueous THF solution andacidification with dilute hydrochloric acid solution should yield theamide carboxylic acid (step b). This acid can be further treated withBoc anhydride (Boc₂O) in THF in the presence of pyridine, followed by asolution of ammonia in THF at 0 degrees to ambient temperature to yieldthe carboxamido compound (step c).

Scheme 4 illustrates how the treatment of 4′-benzyloxypropiophenone withethyl-t-butyl oxalate in the presence of an equivalent of base, such aslithium hexamethydilsilazide, should afford, after acidification withhydrochloric acid solution, the diketoester (step a). Removal of thebenzyl group via hydrogenolysis and treatment of the resulting phenolwith ethyl bromoacetate in the presence of a base, such as potassiumcarbonate, in a solvent such as DMF at elevated temperature shouldproduce the ester (step b). Heating this diketo-diester with an arylhydrazine in a solvent such as ethanol should produce the pyrazole esteralong with the uncyclized imine (step c). These materials may beseparated due to their solubility differences, or through flash columnchromatography. The pyrazole, upon treatment with trifluoroacetic acidin methylene chloride, should afford the carboxylic acid (step d).Subsequent conversion of the carboxylic acid to the acid chloride usingthionyl chloride followed by treatment with N-aminopiperidine shouldafford the hydazide ester (step e). Hydrolysis of the ester with lithiumhydroxide in aqueous THF solution, and acidification with dilutehydrochloric acid solution, should yield the hydrazide carboxylic acid(step f). Reaction of this acid with thionyl chloride followed bytreatment with ammonia should afford the carboxamido compound (step g).

Scheme 5 shows how the treatment of 3′-nitropropiophenone with diethyloxalate in the presence of base, such as lithium hexamethydilsilazide,should afford, after acidification with hydrochloric acid solution, thediketo-ester (step a). Heating this ester with an aryl hydrazine in asolvent such as ethanol should produce the pyrazole ester along with theuncyclized imine (step b). These materials may be separated due to theirsolubility differences, or heated together in ethanolic hydroxidesolution to cause further conversion of the imine to the pyrazole alongwith concomitant saponification of the ester to the carboxylic acid(step c). Subsequent conversion of the carboxylic acid to the acidchloride using thionyl chloride followed by treatment withN-aminopiperidine should afford the hydazide (step d). The nitrocompound can be reduced to the aniline using sodium dithionite inaqueous dioxane containing concentrated ammonium hydroxide solution togive the aniline (step e). Reaction of the aniline with ethyl4-bromocrotonate in acetone at reflux in the presence of potassiumcarbonate should afford the ester (step f). Hydrolysis of the ester withlithium hydroxide in aqueous THF solution, and acidification with dilutehydrochloric acid solution should yield the hydrazide carboxylic acid(step g).

Alternatively, the aniline can be treated with ethyl malonyl chloride inthe presence of base to yield the ester (step h). The ester can then behydrolyzed with lithium hydroxide in aqueous THF solution, and afteracidification with dilute hydrochloric acid solution should yield thehydrazide carboxylic acid (step i).

Scheme 6 describes how the conversion of the carboxylic acid of Scheme 5to its acid chloride using thionyl chloride followed by treatment withN-aminopiperidine should afford the hydazide (step a). The nitrocompound can be reduced to the aniline using sodium dithionite inaqueous dioxane containing concentrated ammonium hydroxide solution togive the aniline (step b). Reaction of the aniline with methanesulfonylchloride in the presence of base should afford the sulfonamide (step c).

Scheme 7 depicts how the condensation of a propiophenone withethyl-t-butyl oxalate in the presence of base, such as lithiumhexamethydilsilazide, should afford, after acidification withhydrochloric acid solution, the diketo-ester (step a). Heating thisdiketo-ester with an aryl hydrazine in a solvent such as ethanol shouldproduce the pyrazole ester which can be separated from the uncyclizedimine via their solubility differences or through flash chromatography(step b). The pyrazole, upon treatment with trifluoroacetic acid inmethylene chloride, should afford the carboxylic acid (step c).Subsequent conversion of the carboxylic acid to the acid chloride usingthionyl chloride followed by treatment with N-aminopiperidine shouldafford the hydazide ester (step d). Hydrolysis of the remaining esterwith lithium hydroxide in aqueous THF solution, and acidification withdilute hydrochloric acid solution should yield the hydrazide carboxylicacid (step e). The carboxylic acid can then be treated with thionylchloride followed by ammonia to produce the carboxamido compound (stepf).

Scheme 8 illustrates how the Reaction of a propiophenone withethyl-t-butyl oxalate in the presence of base, such as lithiumhexamethydilsilazide, should afford, after acidification withhydrochloric acid solution, the diketo-ester (step a). Heating thisdiketo-ester with an aryl hydrazine in a solvent such as ethanol shouldproduce the pyrazole ester which can be separated from the uncyclizedimine via their solubility differences or through flash chromatography(step b). The pyrazole, upon treatment with trifluoroacetic acid inmethylene chloride, should afford the carboxylic acid (step c).Subsequent conversion of the carboxylic acid to the acid chloride usingthionyl chloride followed by treatment with N-aminopiperidine shouldafford the hydazide ester (step d). Hydrolysis of the remaining esterwith lithium hydroxide in aqueous THF solution, and acidification withdilute hydrochloric acid solution should yield the hydrazide carboxylicacid (step e). The carboxylic acid can then be treated with thionylchloride followed by ammonia, or with Boc anhydride (Boc₂O) in THF inthe presence of pyridine, followed by a solution of ammonia in THF at 0degrees to ambient temperature to produce the benzamide (step f).

Scheme 9 shows how the treatment of a propiophenone with ethyl-t-butyloxalate in the presence of base, such as lithium hexamethydilsilazide,should afford, after acidification with hydrochloric acid solution, thediketo-ester (step a). Heating this diketo-ester with a hydrazine of anethyl aryloxyacetate in a solvent such as ethanol should produce thepyrazole ester which can be separated from the uncyclized imine viatheir solubility differences or through flash chromatography (step b).The pyrazole, upon treatment with trifluoroacetic acid in methylenechloride, should afford the carboxylic acid (step c). Subsequentconversion of the carboxylic acid to the acid chloride using thionylchloride followed by treatment with N-aminopiperidine should afford thehydazide ester (step d). Hydrolysis of the remaining ester with lithiumhydroxide in aqueous THF solution, and acidification with dilutehydrochloric acid solution should yield the hydrazide carboxylic acid(step e). The carboxylic acid can then be treated with thionyl chloridefollowed by ammonia to produce the aryloxyacetamide (step f).

Scheme 10 describes how the treatment of a propiophenone withdiethyloxalate in the presence of base, such as lithiumhexamethydilsilazide, should afford, after acidification withhydrochloric acid solution, the diketo-ester (step a). Heating thisdiketo-ester with a hydrazine of an arylnitrile in a solvent such asethanol should produce the pyrazole ester which can be separated fromthe uncyclized imine via their solubility differences or through flashchromatography (step b). The pyrazole, upon treatment with lithiumhydroxide in aqueous THF solution, and acidification with dilutehydrochloric acid solution should afford the carboxylic acid (step c).Subsequent conversion of the carboxylic acid to the acid chloride usingthionyl chloride followed by treatment with N-aminopiperidine shouldafford the hydazide ester (step d). Heating a mixture of the arylnitrilewith sodium azide and zinc chloride or zinc bromide in water withvigorous stirring should produce the aryl-tetrazole, after acidificationwith dilute hydrochloric acid solution. Alternatively, the nitrile canbe treated with HCl gas in a solution of chloroform and methanol atabout minus 15 to 0 degrees C. to form the imidate ester which canimmediately be converted to the carboxamidine by subsequent treatmentwith ammonium carbonate in methanol.

Scheme 11 depicts how the reaction of ethyl benzoylacetate withethyl-t-butyl oxalate in the presence of base, such as lithiumhexamethydilsilazide, should afford, after acidification withhydrochloric acid solution, the diketo-diester (step a). Heating thisdiketo-diester with an aryl hydrazine in a solvent such as ethanolshould produce the pyrazole ester which can be separated from theuncyclized imine via their solubility differences or through flashchromatography (step b). The pyrazole, upon treatment withtrifluoroacetic acid in methylene chloride, should afford the carboxylicacid (step c). Subsequent conversion of the carboxylic acid to the acidchloride using thionyl chloride followed by treatment withN-aminopiperidine should afford the hydrazide ester (step d). Hydrolysisof the remaining ester with lithium hydroxide in aqueous THF solution,and acidification with dilute hydrochloric acid solution should yieldthe hydrazide carboxylic acid (step e). The carboxylic acid can then betreated with thionyl chloride followed by ammonia, or with Boc anhydride(Boc₂O) in THF in the presence of pyridine, followed by a solution ofammonia in THF at 0 degrees to ambient temperature to produce thecarboxamido hydrazide (step f).

One stereoisomer of a compound of the present invention may be a morepotent cannabinoid receptor antagonist than its counterpart(s). Thus,stereoisomers are included in the present invention. When required,separation of the racemic material can be achieved by HPLC using achiral column or by a resolution using a resolving agent such asdescribed in Wilen, S. H. Tables of Resolving Agents and OpticalResolutions 1972, 308 or using enantiomerically pure acids and bases. Achiral compound of the present invention may also be directlysynthesized using a chiral catalyst or a chiral ligand, e.g., Jacobsen,E. Acc. Chem. Res. 2000, 33, 421-431 or using other enantio- anddiastereo-selective reactions and reagents known to one skilled in theart of asymmetric synthesis.

Other features of the invention will become apparent in the course ofthe following descriptions of exemplary embodiments that are given forillustration of the invention and are not intended to be limitingthereof.

EXAMPLES

Tables A-E below describe selected examples of the present inventionthat have been synthesized and tested. The activities of these compoundsare as follows:

-   -   +=an IC50 of ≦10 μM;    -   ++=IC50 of ≦1 μM; and,    -   +++=an IC50 ≦100 nM.

The compounds can be prepared according to the methods of the schemenumbers provided for each example.

TABLE A

Number R′ CB1 Receptor Activity NMR (ppm) CDCl₃ or as indicatedSynthetic Route A-1 CH₂CO₂Et + ester-CH₃ 1.26(3H, t) Scheme 3 ring-CH₃2.35(3H, s) ester-CH₂/NH—CH₂ 4.20-4.27(4H, m) aromatic H's 7.05-7.43(7H)A-2 CH(CH₂C₆H₅)CO₂Et ++ ester-CH₃ 1.22(3H, t) Scheme 3 ring-CH₃ 2.35(3H,s) Ph-CH₂ 3.20(2H, d) ester-CH₂ 4.15(2H, q) NH—CH 5.02(1H, m) aromaticH's 7.04-7.45(12H) A-3 CH₂CH₂CO₂Et + ester-CH₃ 1.25(3H, t) Scheme 3ring-CH₃ 2.37(3H, s) CO—CH₂ 2.65(2H, t) NH—CH₂ 3.70(2H, m) ester-CH₂4.15(2H, q) NH—CH 5.02(1H, m) aromatic H's 7.04-7.42(7H) A-4CH(CH₂C₆H₅)CO₂H + DMSO(d6) Scheme 3 ring-CH₃ 2.25(3H, s) Ph-CH₂ 3.16(2H,m) NH—CH 4.21(1H, m) aromatic H's 7.09-7.67(12H) A-5 CH₂CH₂CH₂CO₂Et +ester-CH₃ 1.26(3H, t) Scheme 3 —CHCH₃— 1.33(3H, d) ring-CH₃ 2.36(3H, s)CO—CH₂ 2.62(2H, m) ester-CH₂ 4.14(2H, q) NH—CH 4.56(1H, m) aromatic H's7.05-7.45(7H) A-6 CH(CH₃)CH₂CO₂Et ++ ester-CH₃ 1.26(3H, t) Scheme 3CHCH₃ 1.33(3H, d) ring-CH₃ 2.37(3H, s) CO—CH₂ 2.41(2H, t) NH—CH₂2.62(2H, dds) ester-CH₂ 4.14(2H, q) CHCH₃ 4.56(3H, m) aromatic H's7.05-7.45(7H) A-7 CH(CH₃)CO₂Et ++ ester-CH₃ 1.28(3H, t) Scheme 3 CHCH₃1.51(3H, d) ring-CH₃ 2.36(3H, s) CO—CH₂ 2.41(2H, t) ester-CH₂ 4.23(2H,q) NH—CH 4.76(1H, m) aromatic H's 7.05-7.42(7H) A-8 CH(CH₂CH(CH₃)₂)CO₂Et+++ CH(CH₃)₂ 0.95(6H, t) Scheme 3 ester-CH₃ 1.27(3H, t) CHCH₂1.60-1.77(3H, m) ring-CH₃ 2.36(3H, s) ester-CH₂ 4.21(2H, q) NH—CH4.81(1H, m) aromatic H's 7.04-7.42(7H) A-9 CH(CH₂CH(CH₃)₂)CO₂H ++ CD₃ODScheme 3 CH(CH₃)₂ 0.99(6H, d) CHCH₂ 1.73-1.80(3H, m) ring-CH₃ 2.31(3H,s) ester-CH₂ 4.21(2H, q) NH—CH 4.67(1H, m) aromatic H's 7.19-7.57(7H)A-10 CH(CH(CH₃)CH₂CH₃)—CO₂Et +++ 2(CH₃) 0.95(6H, m) Scheme 3 ester-CH₃1.26(3H, t) CH₂—CH₃ 1.26(2H, m) CH—CH 1.52(1H, m) CHCH₂ 1.60-1.77(3H, m)ring-CH₃ 2.36(3H, s) ester-CH₂ 4.22(2H, q) NH—CH 4.75, 4.8(1H, dd)aromatic H's 7.04-7.42(7H) A-11 CH(C(CH₃)₃)CO₂Et +++ (CH₃)₃ 1.06(9H, s)Scheme 3 ester-CH₃ 1.28(3H, t) ring-CH₃ 2.35(3H, s) ester-CH₂ 4.21(2H,m) NH—CH 4.63(1H, d) aromatic H's 7.04-7.42(7H) A-12 CH(C(CH₃)₃)CO₂H +++CD₃OD Scheme 3 (CH₃)₃ 1.07(9H, s) ring-CH₃ 2.31(3H, s) NH—CH 4.47(1H, s)aromatic H's 7.20-7.59(7H)

TABLE B

Number R′ CB1 Receptor Activity NMR(ppm) Solvent as indicated SyntheticRoute B-1 CH₂CH₂CONH₂ + CD₃OD Scheme 3 ring-CH₃ 2.31(3H, s) CO—CH₂2.54(2H, t) NH—CH₂ 3.63(2H, t) aromatic H's 7.18-7.63(7H) B-2CH(CH₃)CH₂CONH₂ + CD₃OD Scheme 3 CH₃ 1.30(3H, d) ring-CH₃ 2.30(3H, s)CO—CH₂ 2.50(2H, dds) NH—CH 4.48(1H, m) aromatic H's 7.18-7.56(7H) B-3CH(CH₂CH(CH₃)₂)CONH₂ ++ CD₃OD Scheme 3 CH₃ 0.90(6H, d) CH₂CH 1.71(3H, m)ring-CH₃ 2.31(3H, s) NH—CH 4.65(1H, m) aromatic H's 7.19-7.57(7H) B-4CH(CH(CH₃)CH₂CH₃)CONH₂ +++ CD₃OD Scheme 3 CH₃ 0.90-1.10(6H, m) CH₂CH1.20-1.35(2H, m) CH₂CH 1.45-1.60(1H, m) ring-CH₃ 2.36(3H, s) NH—CH 4.50,4.64(d t) aromatic H's 7.05-7.45(7H) B-5 CH(CH₂C₆H₅)CONH₂ +++ CD₃ODScheme 3 ring-CH₃ 2.29(3H, s) PhCH₂ 3.05, 3.25(2H, dm) NH—CH 4.83(1H, m)aromatic H's 7.16-7.60(12H) B-6 CH₂C₆H₅CONH₂(3) ++ DMSO(d6) Scheme 3ring-CH₃ 2.25(3H, s) PhCH₂ 4.46(2H, d) aromatic H's 7.23-7.87(11H) B-7CH₂C₆H₅CONH₂(4) ++ CD₃OD Scheme 3 ring-CH₃ 2.32(3H, s) PhCH₂ 4.61(2H, s)aromatic H's 7.19-7.87(11H) B-8 CH₂C₆H₅C(NH)NH₂(3) ++ CD₃OD Scheme 3ring-CH₃ 2.36(3H, s) PhCH₂ 4.61(2H, s) aromatic H's 7.17-7.90(11H) B-9CH₂C₆H₅C(NH)NH₂(4) + CD₃OD Scheme 3 ring-CH₃ 2.31(3H, s) PhCH₂ 4.66(2H,s) aromatic H's 7.19-7.82(11H) B-10 CH(C(CH₃)₃)CONH₂ +++ CDCl₃ Scheme 3(CH₃)₃ 1.11(9H, s) ring-CH₃ 2.34(3H, s) PhCH₂ 4.52(2H, d) aromatic H's7.04-7.62(11H)

TABLE C

Number Z Y CB1 Receptor Activity NMR(ppm) CDCl₃ unless otherwiseindicated Synthesis Route C-1 3-CO₂Et Cl ++ ester-CH₃ 1.25(3H, t) Scheme1 ring-H 1.41(1H, m) ring-H 1.81(2H, m) ring-H 2.00(1H, brd d) ring-CH₃2.35(3H, s) ring-H 2.58(1H, m) ring-H 2.70.(1H, t) ring-H 2.83(1H, m)ring-H 3.24(1H, brd d) ring-H 3.49(1H, brd d) ester-CH₂ 4.13(2H, q)aromatic H's 7.04-7.80(7H) C-2 4-CO₂Et Cl ++ ester-CH₃ 1.26(3H, t)Scheme 1 ring-H 2.00(4H, m) ring-H 2.33(1H, m) ring-CH₃ 2.36(3H, s)ring-H 2.72.(2H, m) ring-H 3.20(2H, m) ester-CH₂ 4.14(2H, q) aromaticH's 7.04-7.80(7H) C-3 3-CONH₂ Cl +++ CD₃OD Scheme 1 ring-H 1.26(1H, m)ring-H 1.80(3H, m) ring-CH₃ 2.35(3H, s) ring-H 2.68(1H, m) ring-H2.80(1H, m) ring-H 2.92(1H, m) ring-H 2.98.(1H, m) ring-H 3.07(1H, brdd) aromatic H's 7.20-7.60(7H) C-4 4-CO₂Et OCH₃ ester-CH₃ 1.26(3H, t)Scheme 1 ring-H 2.00(4H, m) ring-H 2.33(1H, m) ring-CH₃ 2.36(3H, s)ring-H 2.72.(2H, m) ring-H 3.20(2H, m) OCH₃ 3.79(3H, s) ester-CH₂4.14(2H, q) aromatic H's 6.80-7.50(7H)

TABLE D

CB1 Num- Receptor NMR(ppm) Synthesis ber Q″ n Activity CDCl₃ Route D-1OEt 2 ++ ester-CH₃ 1.27(3H, t) Scheme 2 ring-H 1.60(6H, brd m) ring-H1.94.(2H, m) ring-H 2.17(2H, m) ring-CH₃ 2.34(3H, s) ester-CH₂ 4.23(2H,q) aromatic H's 7.03-7.45(7H)

TABLE E

Num- CB1 Receptor Synthesis ber Z Activity NMR(ppm) Route E-1 4-CO₂Et +CDCl₃ Scheme 2 ester-CH₃ 1.25(3H, t) ring-H 1.70(4H, brd m) ring-H1.80(2H, m) ring-H 1.97(2H, m) ring-CH₃ 2.37(3H, s) ring-H 2.50(1H, m)ring-H 4.13(1H, m) ester-CH₂ 4.13(2H, q) aromatic H's 6.93-7.42(7H) E-24-CONH₂ + CD₃OD Scheme 2 ring-H 1.75(4H, brd m) ring-H 1.86(4H, brd m)ring-CH₃ 2.31(3H, s) ring-H 2.39(1H, m) ring-H 4.15(1H, m) aromatic H's7.17-7.60(7H)

Tables 1a-6b show representative examples of the compounds of thepresent invention. Each example in the tables represents an individualspecies of the present invention.

TABLE 1a

Ex. # Y Z (position on ring) Q n 1 Cl 2-CO₂Et N 1 2 Cl 2-CO₂H N 1 3 Cl2-CH₂CO₂Et N 1 4 Cl 2-CH₂CO₂H N 1 5 CH₃ 2-CO₂Et N 1 6 CH₃ 2-CO₂H N 1 7CH₃ 2-CH₂CO₂Et N 1 8 CH₃ 2-CH₂CO₂H N 1 9 OCH₃ 2-CO₂Et N 1 10 OCH₃ 2-CO₂HN 1 11 OCH₃ 2-CH₂CO₂Et N 1 12 OCH₃ 2-CH₂CO₂H N 1 13 CH(CH₃)₂ 2-CO₂Et N 114 CH(CH₃)₂ 2-CO₂H N 1 15 CH(CH₃)₂ 2-CH₂CO₂Et N 1 16 CH(CH₃)₂ 2-CH₂CO₂HN 1 17 Cl 2-CO₂Et N 2 18 Cl 2-CO₂H N 2 19 Cl 2-CH₂CO₂Et N 2 20 Cl2-CH₂CO₂H N 2 21 CH₃ 2-CO₂Et N 2 22 CH₃ 2-CO₂H N 2 23 CH₃ 2-CH₂CO₂Et N 224 CH₃ 2-CH₂CO₂H N 2 25 OCH₃ 2-CO₂Et N 2 26 OCH₃ 2-CO₂H N 2 27 OCH₃2-CH₂CO₂Et N 2 28 OCH₃ 2-CH₂CO₂H N 2 29 CH(CH₃)₂ 2-CO₂Et N 2 30 CH(CH₃)₂2-CO₂H N 2 31 CH(CH₃)₂ 2-CH₂CO₂Et N 2 32 CH(CH₃)₂ 2-CH₂CO₂H N 2 33 Cl3-CO₂Et N 1 34 Cl 3-CO₂H N 1 35 Cl 3-CH₂CO₂Et N 1 36 Cl 3-CH₂CO₂H N 1 37CH₃ 3-CO₂Et N 1 38 CH₃ 3-CO₂H N 1 39 CH₃ 3-CH₂CO₂Et N 1 40 CH₃ 3-CH₂CO₂HN 1 41 OCH₃ 3-CO₂Et N 1 42 OCH₃ 3-CO₂H N 1 43 OCH₃ 3-CH₂CO₂Et N 1 44OCH₃ 3-CH₂CO₂H N 1 45 CH(CH₃)₂ 3-CO₂Et N 1 46 CH(CH₃)₂ 3-CO₂H N 1 47CH(CH₃)₂ 3-CH₂CO₂Et N 1 48 CH(CH₃)₂ 3-CH₂CO₂H N 1 49 Cl 3-CO₂Et N 2 50Cl 3-CO₂H N 2 51 Cl 3-CH₂CO₂Et N 2 52 Cl 3-CH₂CO₂H N 2 53 CH₃ 3-CO₂Et N2 54 CH₃ 3-CO₂H N 2 55 CH₃ 3-CH₂CO₂Et N 2 56 CH₃ 3-CH₂CO₂H N 2 57 OCH₃3-CO₂Et N 2 58 OCH₃ 3-CO₂H N 2 59 OCH₃ 3-CH₂CO₂Et N 2 60 OCH₃ 3-CH₂CO₂HN 2 61 CH(CH₃)₂ 3-CO₂Et N 2 62 CH(CH₃)₂ 3-CO₂H N 2 63 CH(CH₃)₂3-CH₂CO₂Et N 2 64 CH(CH₃)₂ 3-CH₂CO₂H N 2 65 Cl 4-CO₂Et N 2 66 Cl 4-CO₂HN 2 67 Cl 4-CH₂CO₂Et N 2 68 Cl 4-CH₂CO₂H N 2 69 CH₃ 4-CO₂Et N 2 70 CH₃4-CO₂H N 2 71 CH₃ 4-CH₂CO₂Et N 2 72 CH₃ 4-CH₂CO₂H N 2 73 OCH₃ 4-CO₂Et N2 74 OCH₃ 4-CO₂H N 2 75 OCH₃ 4-CH₂CO₂Et N 2 76 OCH₃ 4-CH₂CO₂H N 2 77CH(CH₃)₂ 4-CO₂Et N 2 78 CH(CH₃)₂ 4-CO₂H N 2 79 CH(CH₃)₂ 4-CH₂CO₂Et N 280 CH(CH₃)₂ 4-CH₂CO₂H N 2 81 Cl 1-CO₂Et C 1 82 Cl 1-CO₂H C 1 83 Cl1-CH₂CO₂Et C 1 84 Cl 1-CH₂CO₂H C 1 85 CH₃ 1-CO₂Et C 1 86 CH₃ 1-CO₂H C 187 CH₃ 1-CH₂CO₂Et C 1 88 CH₃ 1-CH₂CO₂H C 1 89 OCH₃ 1-CO₂Et C 1 90 OCH₃1-CO₂H C 1 91 OCH₃ 1-CH₂CO₂Et C 1 92 OCH₃ 1-CH₂CO₂H C 1 93 CH(CH₃)₂1-CO₂Et C 1 94 CH(CH₃)₂ 1-CO₂H C 1 95 CH(CH₃)₂ 1-CH₂CO₂Et C 1 96CH(CH₃)₂ 1-CH₂CO₂H C 1 97 Cl 1-CO₂Et C 2 98 Cl 1-CO₂H C 2 99 Cl1-CH₂CO₂Et C 2 100 Cl 1-CH₂CO₂H C 2 101 CH₃ 1-CO₂Et C 2 102 CH₃ 1-CO₂H C2 103 CH₃ 1-CH₂CO₂Et C 2 104 CH₃ 2-CH₂CO₂H C 2 105 OCH₃ 2-CO₂Et C 2 106OCH₃ 1-CO₂H C 2 107 OCH₃ 1-CH₂CO₂Et C 2 108 OCH₃ 1-CH₂CO₂H C 2 109CH(CH₃)₂ 1-CO₂Et C 2 110 CH(CH₃)₂ 1-CO₂H C 2 111 CH(CH₃)₂ 1-CH₂CO₂Et C 2112 CH(CH₃)₂ 1-CH₂CO₂H C 2 113 Cl 2-CO₂Et CH 1 114 Cl 2-CO₂H CH 1 115 Cl2-CH₂CO₂Et CH 1 116 Cl 2-CH₂CO₂H CH 1 117 CH₃ 2-CO₂Et CH 1 118 CH₃2-CO₂H CH 1 119 CH₃ 2-CH₂CO₂Et CH 1 120 CH₃ 2-CH₂CO₂H CH 1 121 OCH₃2-CO₂Et CH 1 122 OCH₃ 2-CO₂H CH 1 123 OCH₃ 2-CH₂CO₂Et CH 1 124 OCH₃2-CH₂CO₂H CH 1 125 CH(CH₃)₂ 2-CO₂Et CH 1 126 CH(CH₃)₂ 2-CO₂H CH 1 127CH(CH₃)₂ 2-CH₂CO₂Et CH 1 128 CH(CH₃)₂ 2-CH₂CO₂H CH 1 129 Cl 2-CO₂Et CH 2130 Cl 2-CO₂H CH 2 131 Cl 2-CH₂CO₂Et CH 2 132 Cl 2-CH₂CO₂H CH 2 133 CH₃2-CO₂Et CH 2 134 CH₃ 2-CO₂H CH 2 135 CH₃ 2-CH₂CO₂Et CH 2 136 CH₃2-CH₂CO₂H CH 2 137 OCH₃ 2-CO₂Et CH 2 138 OCH₃ 2-CO₂H CH 2 139 OCH₃2-CH₂CO₂Et CH 2 140 OCH₃ 2-CH₂CO₂H CH 2 141 CH(CH₃)₂ 2-CO₂Et CH 2 142CH(CH₃)₂ 2-CO₂H CH 2 143 CH(CH₃)₂ 2-CH₂CO₂Et CH 2 144 CH(CH₃)₂ 2-CH₂CO₂HCH 2

TABLE 1b

Ex. # Y Z (position on ring) Q n 1 Cl 2-CH₂OCH₂CO₂Et N 1 2 Cl2-CH₂OCH₂CO₂H N 1 3 Cl 2-CH₂O(CH₂)₃PO(OEt)₂ N 1 4 Cl 2-CH₂O(CH₂)₃PO(OH)₂N 1 5 CH₃ 2-CH₂OCH₂CO₂Et N 1 6 CH₃ 2-CH₂OCH₂CO₂H N 1 7 CH₃2-CH₂O(CH₂)₃PO(OEt)₂ N 1 8 CH₃ 2-CH₂O(CH₂)₃PO(OH)₂ N 1 9 OCH₃2-CH₂OCH₂CO₂Et N 1 10 OCH₃ 2-CH₂OCH₂CO₂H N 1 11 OCH₃2-CH₂O(CH₂)₃PO(OEt)₂ N 1 12 OCH₃ 2-CH₂O(CH₂)₃PO(OH)₂ N 1 13 CH(CH₃)₂2-CH₂OCH₂CO₂Et N 1 14 CH(CH₃)₂ 2-CH₂OCH₂CO₂H N 1 15 CH(CH₃)₂2-CH₂O(CH₂)₃PO(OEt)₂ N 1 16 CH(CH₃)₂ 2-CH₂O(CH₂)₃PO(OH)₂ N 1 17 Cl2-CH₂OCH₂CO₂Et N 2 18 Cl 2-CH₂OCH₂CO₂H N 2 19 Cl 2-CH₂O(CH₂)₃PO(OEt)₂ N2 20 Cl 2-CH₂O(CH₂)₃PO(OH)₂ N 2 21 CH₃ 2-CH₂OCH₂CO₂Et N 2 22 CH₃2-CH₂OCH₂CO₂H N 2 23 CH₃ 2-CH₂O(CH₂)₃PO(OEt)₂ N 2 24 CH₃2-CH₂O(CH₂)₃PO(OH)₂ N 2 25 OCH₃ 2-CH₂OCH₂CO₂Et N 2 26 OCH₃ 2-CH₂OCH₂CO₂HN 2 27 OCH₃ 2-CH₂O(CH₂)₃PO(OEt)₂ N 2 28 OCH₃ 2-CH₂O(CH₂)₃PO(OH)₂ N 2 29CH(CH₃)₂ 2-CH₂OCH₂CO₂Et N 2 30 CH(CH₃)₂ 2-CH₂OCH₂CO₂H N 2 31 CH(CH₃)₂2-CH₂O(CH₂)₃PO(OEt)₂ N 2 32 CH(CH₃)₂ 2-CH₂O(CH₂)₃PO(OH)₂ N 2 33 Cl3-CH₂OCH₂CO₂Et N 1 34 Cl 3-CH₂OCH₂CO₂H N 1 35 Cl 3-CH₂O(CH₂)₃PO(OEt)₂ N1 36 Cl 3-CH₂O(CH₂)₃PO(OH)₂ N 1 37 CH₃ 3-CH₂OCH₂CO₂Et N 1 38 CH₃3-CH₂OCH₂CO₂H N 1 39 CH₃ 3-CH₂O(CH₂)₃PO(OEt)₂ N 1 40 CH₃3-CH₂O(CH₂)₃PO(OH)₂ N 1 41 OCH₃ 3-CH₂OCH₂CO₂Et N 1 42 OCH₃ 3-CH₂OCH₂CO₂HN 1 43 OCH₃ 3-CH₂O(CH₂)₃PO(OEt)₂ N 1 44 OCH₃ 3-CH₂O(CH₂)₃PO(OH)₂ N 1 45CH(CH₃)₂ 3-CH₂OCH₂CO₂Et N 1 46 CH(CH₃)₂ 3-CH₂OCH₂CO₂H N 1 47 CH(CH₃)₂3-CH₂O(CH₂)₃PO(OEt)₂ N 1 48 CH(CH₃)₂ 3-CH₂O(CH₂)₃PO(OH)₂ N 1 49 Cl3-CH₂OCH₂CO₂Et N 2 50 Cl 3-CH₂OCH₂CO₂H N 2 51 Cl 3-CH₂O(CH₂)₃PO(OEt)₂ N2 52 Cl 3-CH₂O(CH₂)₃PO(OH)₂ N 2 53 CH₃ 3-CH₂OCH₂CO₂Et N 2 54 CH₃3-CH₂OCH₂CO₂H N 2 55 CH₃ 3-CH₂O(CH₂)₃PO(OEt)₂ N 2 56 CH₃3-CH₂O(CH₂)₃PO(OH)₂ N 2 57 OCH₃ 3-CH₂OCH₂CO₂Et N 2 58 OCH₃ 3-CH₂OCH₂CO₂HN 2 59 OCH₃ 3-CH₂O(CH₂)₃PO(OEt)₂ N 2 60 OCH₃ 3-CH₂O(CH₂)₃PO(OH)₂ N 2 61CH(CH₃)₂ 3-CH₂OCH₂CO₂Et N 2 62 CH(CH₃)₂ 3-CH₂OCH₂CO₂H N 2 63 CH(CH₃)₂3-CH₂O(CH₂)₃PO(OEt)₂ N 2 64 CH(CH₃)₂ 3-CH₂O(CH₂)₃PO(OH)₂ N 2 65 Cl4-CH₂OCH₂CO₂Et N 2 66 Cl 4-CH₂OCH₂CO₂H N 2 67 Cl 4-CH₂O(CH₂)₃PO(OEt)₂ N2 68 Cl 4-CH₂O(CH₂)₃PO(OH)₂ N 2 69 CH₃ 4-CH₂OCH₂CO₂Et N 2 70 CH₃4-CH₂OCH₂CO₂H N 2 71 CH₃ 4-CH₂O(CH₂)₃PO(OEt)₂ N 2 72 CH₃4-CH₂O(CH₂)₃PO(OH)₂ N 2 73 OCH₃ 4-CH₂OCH₂CO₂Et N 2 74 OCH₃ 4-CH₂OCH₂CO₂HN 2 75 OCH₃ 4-CH₂O(CH₂)₃PO(OEt)₂ N 2 76 OCH₃ 4-CH₂O(CH₂)₃PO(OH)₂ N 2 77CH(CH₃)₂ 4-CH₂OCH₂CO₂Et N 2 78 CH(CH₃)₂ 4-CH₂OCH₂CO₂H N 2 79 CH(CH₃)₂4-CH₂O(CH₂)₃PO(OEt)₂ N 2 80 CH(CH₃)₂ 4-CH₂O(CH₂)₃PO(OH)₂ N 2 81 Cl2-CH₂OCH₂CO₂Et CH 1 82 Cl 2-CH₂OCH₂CO₂H CH 1 83 Cl 2-CH₂O(CH₂)₃PO(OEt)₂CH 1 84 Cl 2-CH₂O(CH₂)₃PO(OH)₂ CH 1 85 CH₃ 2-CH₂OCH₂CO₂Et CH 1 86 CH₃2-CH₂OCH₂CO₂H CH 1 87 CH₃ 2-CH₂O(CH₂)₃PO(OEt)₂ CH 1 88 CH₃2-CH₂O(CH₂)₃PO(OH)₂ CH 1 89 OCH₃ 2-CH₂OCH₂CO₂Et CH 1 90 OCH₃2-CH₂OCH₂CO₂H CH 1 91 OCH₃ 2-CH₂O(CH₂)₃PO(OEt)₂ CH 1 92 OCH₃2-CH₂O(CH₂)₃PO(OH)₂ CH 1 93 CH(CH₃)₂ 2-CH₂OCH₂CO₂Et CH 1 94 CH(CH₃)₂2-CH₂OCH₂CO₂H CH 1 95 CH(CH₃)₂ 2-CH₂O(CH₂)₃PO(OEt)₂ CH 1 96 CH(CH₃)₂2-CH₂O(CH₂)₃PO(OH)₂ CH 1 97 Cl 2-CH₂OCH₂CO₂Et CH 2 98 Cl 2-CH₂OCH₂CO₂HCH 2 99 Cl 2-CH₂O(CH₂)₃PO(OEt)₂ CH 2 100 Cl 2-CH₂O(CH₂)₃PO(OH)₂ CH 2 101CH₃ 2-CH₂OCH₂CO₂Et CH 2 102 CH₃ 2-CH₂OCH₂CO₂H CH 2 103 CH₃2-CH₂O(CH₂)₃PO(OEt)₂ CH 2 104 CH₃ 2-CH₂O(CH₂)₃PO(OH)₂ CH 2 105 OCH₃2-CH₂OCH₂CO₂Et CH 2 106 OCH₃ 2-CH₂OCH₂CO₂H CH 2 107 OCH₃2-CH₂O(CH₂)₃PO(OEt)₂ CH 2 108 OCH₃ 2-CH₂O(CH₂)₃PO(OH)₂ CH 2 109 CH(CH₃)₂2-CH₂OCH₂CO₂Et CH 2 110 CH(CH₃)₂ 2-CH₂OCH₂CO₂H CH 2 111 CH(CH₃)₂2-CH₂O(CH₂)₃PO(OEt)₂ CH 2 112 CH(CH₃)₂ 2-CH₂O(CH₂)₃PO(OH)₂ CH 2 113 Cl1-CH₂OCH₂CO₂Et C 1 114 Cl 1CH₂OCH₂CO₂H C 1 115 Cl 1-CH₂O(CH₂)₃PO(OEt)₂ C1 116 Cl 1-CH₂O(CH₂)₃PO(OH)₂ C 1 117 CH₃ 1-CH₂OCH₂CO₂Et C 1 118 CH₃1-CH₂OCH₂CO₂H C 1 119 CH₃ 1-CH₂O(CH₂)₃PO(OEt)₂ C 1 120 CH₃1-CH₂O(CH₂)₃PO(OH)₂ C 1 121 OCH₃ 1-CH₂OCH₂CO₂Et C 1 122 OCH₃1-CH₂OCH₂CO₂H C 1 123 OCH₃ 1-CH₂O(CH₂)₃PO(OEt)₂ C 1 124 OCH₃1-CH₂O(CH₂)₃PO(OH)₂ C 1 125 CH(CH₃)₂ 1-CH₂OCH₂CO₂Et C 1 126 CH(CH₃)₂1-CH₂OCH₂CO₂H C 1 127 CH(CH₃)₂ 1-CH₂O(CH₂)₃PO(OEt)₂ C 1 128 CH(CH₃)₂1-CH₂O(CH₂)₃PO(OH)₂ C 1 129 Cl 3-CH₂OCH₂CO₂Et CH 1 130 Cl 3-CH₂OCH₂CO₂HCH 2 131 Cl 3-CH₂O(CH₂)₃PO(OEt)₂ CH 2 132 Cl 3-CH₂O(CH₂)₃PO(OH)₂ CH 2133 CH₃ 3-CH₂OCH₂CO₂Et CH 2 134 CH₃ 3-CH₂OCH₂CO₂H CH 2 135 CH₃3-CH₂O(CH₂)₃PO(OEt)₂ CH 2 136 CH₃ 3-CH₂O(CH₂)₃PO(OH)₂ CH 2 137 OCH₃3-CH₂OCH₂CO₂Et CH 2 138 OCH₃ 3-CH₂OCH₂CO₂H CH 2 139 OCH₃3-CH₂O(CH₂)₃PO(OEt)₂ CH 2 140 OCH₃ 3-CH₂O(CH₂)₃PO(OH)₂ CH 2 141 CH(CH₃)₂3-CH₂OCH₂CO₂Et CH 2 142 CH(CH₃)₂ 3-CH₂OCH₂CO₂H CH 2 143 CH(CH₃)₂3-CH₂O(CH₂)₃PO(OEt)₂ CH 2 144 CH(CH₃)₂ 3-CH₂O(CH₂)₃PO(OH)₂ CH 2

TABLE 1c

Ex. # Y Z (position on ring) Q n 1 Cl 2-CONH₂ N 1 2 Cl 2-CH₂OCH₂CONH₂ N1 3 Cl 2-CH₂CONH₂ N 1 4 Cl 2-CH₂OCH₂CH═CHCONH₂ N 1 5 CH₃ 2-CONH₂ N 1 6CH₃ 2-CH₂OCH₂CONH₂ N 1 7 CH₃ 2-CH₂CONH₂ N 1 8 CH₃ 2-CH₂OCH₂CH═CHCONH₂ N1 9 OCH₃ 2-CONH₂ N 1 10 OCH₃ 2-CH₂OCH₂CONH₂ N 1 11 OCH₃ 2-CH₂CONH₂ N 112 OCH₃ 2-CH₂OCH₂CH═CHCONH₂ N 1 13 CH(CH₃)₂ 2-CONH₂ N 1 14 CH(CH₃)₂2-CH₂OCH₂CONH₂ N 1 15 CH(CH₃)₂ 2-CH₂CONH₂ N 1 16 CH(CH₃)₂2-CH₂OCH₂CH═CHCONH₂ N 1 17 Cl 2-CONH₂ N 2 18 Cl 2-CH₂OCH₂CONH₂ N 2 19 Cl2-CH₂CONH₂ N 2 20 Cl 2-CH₂OCH₂CH═CHCONH₂ N 2 21 CH₃ 2-CONH₂ N 2 22 CH₃2-CH₂OCH₂CONH₂ N 2 23 CH₃ 2-CH₂CONH₂ N 2 24 CH₃ 2-CH₂OCH₂CH═CHCONH₂ N 225 OCH₃ 2-CONH₂ N 2 26 OCH₃ 2-CH₂OCH₂CONH₂ N 2 27 OCH₃ 2-CH₂CONH₂ N 2 28OCH₃ 2-CH₂OCH₂CH═CHCONH₂ N 2 29 CH(CH₃)₂ 2-CONH₂ N 2 30 CH(CH₃)₂2-CH₂OCH₂CONH₂ N 2 31 CH(CH₃)₂ 2-CH₂CONH₂ N 2 32 CH(CH₃)₂2-CH₂OCH₂CH═CHCONH₂ N 2 33 Cl 3-CONH₂ N 1 34 Cl 3-CH₂OCH₂CONH₂ N 1 35 Cl3-CH₂CONH₂ N 1 36 Cl 3-CH₂OCH₂CH═CHCONH₂ N 1 37 CH₃ 3-CONH₂ N 1 38 CH₃3-CH₂OCH₂CONH₂ N 1 39 CH₃ 3-CH₂CONH₂ N 1 40 CH₃ 3-CH₂OCH₂CH═CHCONH₂ N 141 OCH₃ 3-CONH₂ N 1 42 OCH₃ 3-CH₂OCH₂CONH₂ N 1 43 OCH₃ 3-CH₂CONH₂ N 1 44OCH₃ 3-CH₂OCH₂CH═CHCONH₂ N 1 45 CH(CH₃)₂ 3-CONH₂ N 1 46 CH(CH₃)₂3-CH₂OCH₂CONH₂ N 1 47 CH(CH₃)₂ 3-CH₂CONH₂ N 1 48 CH(CH₃)₂3-CH₂OCH₂CH═CHCONH₂ N 1 49 Cl 3-CONH₂ N 2 50 Cl 3-CH₂OCH₂CONH₂ N 2 51 Cl3-CH₂CONH₂ N 2 52 Cl 3-CH₂OCH₂CH═CHCONH₂ N 2 53 CH₃ 3-CONH₂ N 2 54 CH₃3-CH₂OCH₂CONH₂ N 2 55 CH₃ 3-CH₂CONH₂ N 2 56 CH₃ 3-CH₂OCH₂CH═CHCONH₂ N 257 OCH₃ 3-CONH₂ N 2 58 OCH₃ 3-CH₂OCH₂CONH₂ N 2 59 OCH₃ 3-CH₂CONH₂ N 2 60OCH₃ 3-CH₂OCH₂CH═CHCONH₂ N 2 61 CH(CH₃)₂ 3-CONH₂ N 2 62 CH(CH₃)₂3-CH₂OCH₂CONH₂ N 2 63 CH(CH₃)₂ 3-CH₂CONH₂ N 2 64 CH(CH₃0₂3-CH₂OCH₂CH═CHCONH₂ N 2 65 Cl 4-CONH₂ N 2 66 Cl 4-CH₂OCH₂CONH₂ N 2 67 Cl4-CH₂CONH₂ N 2 68 Cl 4-CH₂OCH₂CH═CHCONH₂ N 2 69 CH₃ 4-CONH₂ N 2 70 CH₃4-CH₂OCH₂CONH₂ N 2 71 CH₃ 4-CH₂CONH₂ N 2 72 CH₃ 4-CH₂OCH₂CH═CHCONH₂ N 273 OCH₃ 4-CONH₂ N 2 74 OCH₃ 4-CH₂OCH₂CONH₂ N 2 75 OCH₃ 4-CH₂CONH₂ N 2 76OCH₃ 4-CH₂OCH₂CH═CHCONH₂ N 2 77 CH(CH₃)₂ 4-CONH₂ N 2 78 CH(CH₃)₂4-CH₂OCH₂CONH₂ N 2 79 CH(CH₃)₂ 4-CH₂CONH₂ N 2 80 CH(CH₃)₂4-CH₂OCH₂CH═CHCONH₂ N 2 81 Cl 1-CONH₂ C 1 82 Cl 1-CH₂OCH₂CONH₂ C 1 83 Cl1-CH₂CONH₂ C 1 84 CH₃ 1-CONH₂ C 1 85 CH₃ 1-CH₂OCH₂CONH₂ C 1 86 CH₃1-CH₂CONH₂ C 1 87 OCH₃ 1-CONH₂ C 1 88 OCH₃ 1-CH₂OCH₂CONH₂ C 1 89 OCH₃1-CH₂CONH₂ C 1 90 CH(CH₃)₂ 1-CONH₂ C 1 91 CH(CH₃)₂ 1-CH₂OCH₂CONH₂ C 1 92CH(CH₃)₂ 1-CH₂CONH₂ C 1 93 Cl 1-CONH₂ C 2 94 Cl 1-CH₂OCH₂CONH₂ C 2 95 Cl1-CH₂CONH₂ C 2 96 CH₃ 1-CONH₂ C 2 97 CH₃ 1-CH₂OCH₂CONH₂ C 2 98 CH₃1-CH₂CONH₂ C 2 99 OCH₃ 1-CONH₂ C 2 100 OCH₃ 1-CH₂OCH₂CONH₂ C 2 101 OCH₃1-CH₂CONH₂ C 2 102 CH(CH₃)₂ 1-CONH₂ C 2 103 CH(CH₃)₂ 1-CH₂OCH₂CONH₂ C 2104 CH(CH₃)₂ 1-CH₂CONH₂ C 2 105 Cl 2-CONH₂ CH 1 106 Cl 2-CH₂OCH₂CONH₂ CH1 107 Cl 2-CH₂CONH₂ CH 1 108 Cl 2-CH₂OCH₂CH═CHCONH₂ CH 1 109 CH₃ 2-CONH₂CH 1 110 CH₃ 2-CH₂OCH₂CONH₂ CH 1 111 CH₃ 2-CH₂CONH₂ CH 1 112 CH₃2-CH₂OCH₂CH═CHCONH₂ CH 1 113 OCH₃ 2-CONH₂ CH 1 114 OCH₃ 2-CH₂OCH₂CONH₂CH 1 115 OCH₃ 2-CH₂CONH₂ CH 1 116 OCH₃ 2-CH₂OCH₂CH═CHCONH₂ CH 1 117CH(CH₃)₂ 2-CONH₂ CH 1 118 CH(CH₃)₂ 2-CH₂OCH₂CONH₂ CH 1 119 CH(CH₃)₂2-CH₂CONH₂ CH 1 120 CH(CH₃)₂ 2-CH₂OCH₂CH═CHCONH₂ CH 1 121 Cl 2-CONH₂ CH2 122 Cl 2-CH₂OCH₂CONH₂ CH 2 123 Cl 2-CH₂CONH₂ CH 2 124 Cl2-CH₂OCH₂CH═CHCONH₂ CH 2 125 CH₃ 2-CONH₂ CH 2 126 CH₃ 2-CH₂OCH₂CONH₂ CH2 127 CH₃ 2-CH₂CONH₂ CH 2 128 CH₃ 2-CH₂OCH₂CH═CHCONH₂ CH 2 129 OCH₃2-CONH₂ CH 2 130 OCH₃ 2-CH₂OCH₂CONH₂ CH 2 131 OCH₃ 2-CH₂CONH₂ CH 2 132OCH₃ 2-CH₂OCH₂CH═CHCONH₂ CH 2 133 CH(CH₃)₂ 2-CONH₂ CH 2 134 CH(CH₃)₂2-CH₂OCH₂CONH₂ CH 2 135 CH(CH₃)₂ 2-CH₂CONH₂ CH 2 136 CH(CH₃)₂2-CH₂OCH₂CH═CHCONH₂ CH 2 137 Cl 3-CONH₂ CH 1 138 Cl 3-CH₂OCH₂CONH₂ CH 1139 Cl 3-CH₂CONH₂ CH 1 140 Cl 3-CH₂OCH₂CH═CHCONH₂ CH 1 141 CH₃ 3-CONH₂CH 1 142 CH₃ 3-CH₂OCH₂CONH₂ CH 1 143 CH₃ 3-CH₂CONH₂ CH 1 144 CH₃3-CH₂OCH₂CH═CHCONH₂ CH 1 145 OCH₃ 3-CONH₂ CH 1 146 OCH₃ 3-CH₂OCH₂CONH₂CH 1 147 OCH₃ 3-CH₂CONH₂ CH 1 148 OCH₃ 3-CH₂OCH₂CH═CHCONH₂ CH 1 149CH(CH₃)₂ 3-CONH₂ CH 1 150 CH(CH₃)₂ 3-CH₂OCH₂CONH₂ CH 1 151 CH(CH₃)₂3-CH₂CONH₂ CH 1 153 CH(CH₃)₂ 3-CH₂OCH₂CH═CHCONH₂ CH 1 154 Cl 4-CONH₂ CH2 155 Cl 4-CH₂OCH₂CONH₂ CH 2 156 Cl 4-CH₂CONH₂ CH 2 157 Cl4-CH₂OCH₂CH═CHCONH₂ CH 2 158 CH₃ 4-CONH₂ CH 2 159 CH₃ 4-CH₂OCH₂CONH₂ CH2 160 CH₃ 4-CH₂CONH₂ CH 2 161 CH₃ 4-CH₂OCH₂CH═CHCONH₂ CH 2 162 OCH₃4-CONH₂ CH 2 163 OCH₃ 4-CH₂OCH₂CONH₂ CH 2 164 OCH₃ 4-CH₂CONH₂ CH 2 165OCH₃ 4-CH₂OCH₂CH═CHCONH₂ CH 2 166 CH(CH₃)₂ 4-CONH₂ CH 2 167 CH(CH₃)₂4-CH₂OCH₂CONH₂ CH 2 168 CH(CH₃)₂ 4-CH₂CONH₂ CH 2 169 CH(CH₃)₂4-CH₂OCH₂CH═CHCONH₂ CH 2 170 Cl 4-C(NH)NH₂ N 2 171 Cl 3-C(NH)NH₂ N 2 172Cl 2-C(NH)NH₂ N 1 173 Cl 3-C(NH)NH₂ N 1 174 OCH₃ 4-C(NH)NH₂ N 2 175 OCH₃3-C(NH)NH₂ N 2 176 OCH₃ 2-C(NH)NH₂ N 1 177 OCH₃ 3-C(NH)NH₂ N 1 178 CH₃4-C(NH)NH₂ N 2 179 CH₃ 3-C(NH)NH₂ N 2 180 CH₃ 2-C(NH)NH₂ N 1 181 CH₃3-C(NH)NH₂ N 1 182 CH(CH₃)₂ 4-C(NH)NH₂ N 2 183 CH(CH₃)₂ 3-C(NH)NH₂ N 2184 CH(CH₃)₂ 2-C(NH)NH₂ N 1 185 CH(CH₃)₂ 3-C(NH)NH₂ N 1

TABLE 2a

Ex. # X Y X′ 1 CO₂Et H H 2 CO₂H H H 3 CH₂CO₂Et H H 4 CH₂CO₂H H H 5OCH₂CO₂Et H H 6 OCH₂CO₂H H H 7 OCH₂CH₂CH₂PO(OEt)₂ H H 8OCH₂CH₂CH₂PO(OH)₂ H H 9 OCH₂C₆H₄CO₂Et H H 10 OCH₂C₆H₄CO₂H H H 11NHCH₂CO₂Et H H 12 NHCH₂CO₂H H H 13 NHCH₂CH₂CH₂PO(OEt)₂ H H 14NHCH₂CH₂CH₂PO(OH)₂ H H 15 NHCH₂C₆H₄CO₂Et H H 16 NHCH₂C₆H₄CO₂H H H 17NHCOCH₂CH₂CO₂Et H H 18 NHCOCH₂CH₂CO₂H H H 19 NHSO₂CH₃ H H 20NHCH₂CH═CHCO₂Et H H 21 NHCH₂CH═CHCO₂H H H 22 CONH₂ H H 23 CH₂CONH₂ H H24 OCH₂CONH₂ H H 25 CN₄H H H 26 H CO₂Et H 27 H CO₂H H 28 H CH₂CO₂Et H 29H CH₂CO₂H H 30 H OCH₂CO₂Et H 31 H OCH₂CO₂H H 32 H OCH₂CH₂CH₂PO(OEt)₂ H33 H OCH₂CH₂CH₂PO(OH)₂ H 34 H OCH₂C₆H₄CO₂Et H 35 H OCH₂C₆H₄CO₂H H 36 HNHCH₂CO₂Et H 37 H NHCH₂CO₂H H 38 H NHCH₂CH₂CH₂PO(OEt)₂ H 39 HNHCH₂CH₂CH₂PO(OH)₂ H 40 H NHCH₂C₆H₄CO₂Et H 41 H NHCH₂C₆H₄CO₂H H 42 HNHCOCH₂CH₂CO₂Et H 43 H NHCOCH₂CH₂CO₂H H 44 H NHSO₂CH₃ H 45 HNHCH₂CH═CHCO₂Et H 46 H NHCH₂CH═CHOC₂H H 47 H CONH₂ H 48 H CH₂CONH₂ H 49H OCH₂CONH₂ H 50 H CN₄H H 51 CO₂Et H Cl 52 CO₂H H Cl 53 CH₂CO₂Et H Cl 54CH₂CO₂H H Cl 55 OCH₂CO₂Et H Cl 56 OCH₂CO₂H H Cl 57 OCH₂CH₂CH₂PO(OEt)₂ HCl 58 OCH₂CH₂CH₂PO(OH)₂ H Cl 59 OCH₂C₆H₄CO₂Et H Cl 60 OCH₂C₆H₄CO₂H H Cl61 NHCH₂CO₂Et H Cl 62 NHCH₂CO₂H H Cl 63 NHCH₂CH₂CH₂PO(OEt)₂ H Cl 64NHCH₂CH₂CH₂PO(OH)₂ H Cl 65 NHCH₂C₆H₄CO₂Et H Cl 66 NHCH₂C₆H₄CO₂H H Cl 67NHCOCH₂CH₂CO₂Et H Cl 68 NHCOCH₂CH₂CO₂H H Cl 69 NHSO₂CH₃ H Cl 70NHCH₂CH═CHCO₂Et H Cl 71 NHCH₂CH═CHCO₂H H Cl 72 CONH₂ H Cl 73 CH₂CONH₂ HCl 74 OCH₂CONH₂ H Cl 75 CN₄H H Cl 76 H CO₂Et Cl 77 H CO₂H Cl 78 HCH₂CO₂Et Cl 79 H CH₂CO₂H Cl 80 H OCH₂CO₂Et Cl 81 H OCH₂CO₂H Cl 82 HOCH₂CH₂CH₂PO(OEt)₂ Cl 83 H OCH₂CH₂CH₂PO(OH)₂ Cl 84 H OCH₂C₆H₄CO₂Et Cl 85H OCH₂C₆H₄CO₂H Cl 86 H NHCH₂CO₂Et Cl 87 H NHCH₂CO₂H Cl 88 HNHCH₂CH₂CH₂PO(OEt)₂ Cl 89 H NHCH₂CH₂CH₂PO(OH)₂ Cl 90 H NHCH₂C₆H₄CO₂Et Cl91 H NHCH₂C₆H₄CO₂H Cl 92 H NHCOCH₂CH₂CO₂Et Cl 93 H NHCOCH₂CH₂CO₂H Cl 94H NHSO₂CH₃ Cl 95 H NHCH₂CH═CHCO₂Et Cl 96 H NHCH₂CH═CHCO₂H Cl 97 H CONH₂Cl 98 H CH₂CONH₂ Cl 99 H OCH₂CONH₂ Cl 100 H CN₄H Cl 101 CO₂Et H OCH₃ 102CO₂H H OCH₃ 103 CH₂CO₂Et H OCH₃ 104 CH₂CO₂H H OCH₃ 105 OCH₂CO₂Et H OCH₃106 OCH₂CO₂H H OCH₃ 107 OCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 108 OCH₂CH₂CH₂PO(OH)₂H OCH₃ 109 OCH₂C₆H₄CO₂Et H OCH₃ 110 OCH₂C₆H₄CO₂H H OCH₃ 111 NHCH₂CO₂Et HOCH₃ 112 NHCH₂CO₂H H OCH₃ 113 NHCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 114NHCH₂CH₂CH₂PO(OH)₂ H OCH₃ 115 NHCH₂C₆H₄CO₂Et H OCH₃ 116 NHCH₂C₆H₄CO₂H HOCH₃ 117 NHCOCH₂CH₂CO₂Et H OCH₃ 118 NHCOCH₂CH₂CO₂H H OCH₃ 119 NHSO₂CH₃ HOCH₃ 120 NHCH₂CH═CHCO₂Et H OCH₃ 121 NHCH₂CH═CHCO₂H H OCH₃ 122 CONH₂ HOCH₃ 123 CH₂CONH₂ H OCH₃ 124 OCH₂CONH₂ H OCH₃ 125 CN₄H H OCH₃ 126 HCO₂Et OCH₃ 127 H CO₂H OCH₃ 128 H CH₂CO₂Et OCH₃ 129 H CH₂CO₂H OCH₃ 130 HOCH₂CO₂Et OCH₃ 131 H OCH₂CO₂H OCH₃ 132 H OCH₂CH₂CH₂PO(OEt)₂ OCH₃ 133 HOCH₂CH₂CH₂PO(OH)₂ OCH₃ 134 H OCH₂C₆H₄CO₂Et OCH₃ 135 H OCH₂C₆H₄CO₂H OCH₃136 H NHCH₂CO₂Et OCH₃ 137 H NHCH₂CO₂H OCH₃ 138 H NHCH₂CH₂CH₂PO(OEt)₂OCH₃ 139 H NHCH₂CH₂CH₂PO(OH)₂ OCH₃ 140 H NHCH₂C₆H₄CO₂Et OCH₃ 141 HNHCH₂C₆H₄CO₂H OCH₃ 142 H NHCOCH₂CH₂CO₂Et OCH₃ 143 H NHCOCH₂CH₂CO₂H OCH₃144 H NHSO₂CH₃ OCH₃ 145 H NHCH₂CH═CHCO₂Et OCH₃ 146 H NHCH₂CH═CHCO₂H OCH₃147 H CONH₂ OCH₃ 148 H CH₂CONH₂ OCH₃ 149 H OCH₂CONH₂ OCH₃ 150 H CN₄HOCH₃ 151 CO₂Et H CH₃ 152 CO₂H H CH₃ 153 CH₂CO₂Et H CH₃ 154 CH₂CO₂H H CH₃155 OCH₂CO₂Et H CH₃ 156 OCH₂CO₂H H CH₃ 157 OCH₂CH₂CH₂PO(OEt)₂ H CH₃ 158OCH₂CH₂CH₂PO(OH)₂ H CH₃ 159 OCH₂C₆H₄CO₂Et H CH₃ 160 OCH₂C₆H₄CO₂H H CH₃161 NHCH₂CO₂Et H CH₃ 162 NHCH₂CO₂H H CH₃ 163 NHCH₂CH₂CH₂PO(OEt)₂ H CH₃164 NHCH₂CH₂CH₂PO(OH)₂ H CH₃ 165 NHCH₂C₆H₄CO₂Et H CH₃ 166 NHCH₂C₆H₄CO₂HH CH₃ 167 NHCOCH₂CH₂CO₂Et H CH₃ 168 NHCOCH₂CH₂CO₂H H CH₃ 169 NHSO₂CH₃ HCH₃ 170 NHCH₂CH═CHCO₂Et H CH₃ 171 NHCH₂CH═CHCO₂H H CH₃ 172 CONH₂ H CH₃173 CH₂CONH₂ H CH₃ 174 OCH₂CONH₂ H CH₃ 175 CN₄H H CH₃ 176 H CO₂Et CH₃177 H CO₂H CH₃ 178 H CH₂CO₂Et CH₃ 179 H CH₂CO₂H CH₃ 180 H OCH₂CO₂Et CH₃181 H OCH₂CO₂H CH₃ 182 H OCH₂CH₂CH₂PO(OEt)₂ CH₃ 183 H OCH₂CH₂CH₂PO(OH)₂CH₃ 184 H OCH₂C₆H₄CO₂Et CH₃ 185 H OCH₂C₆H₄CO₂H CH₃ 186 H NHCH₂CO₂Et CH₃187 H NHCH₂CO₂H CH₃ 188 H NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 189 HNHCH₂CH₂CH₂PO(OH)₂ CH₃ 190 H NHCH₂C₆H₄CO₂Et CH₃ 191 H NHCH₂C₆H₄CO₂H CH₃192 H NHCOCH₂CH₂CO₂Et CH₃ 193 H NHCOCH₂CH₂CO₂H CH₃ 194 H NHSO₂CH₃ CH₃195 H NHCH₂CH═CHCO₂Et CH₃ 196 H NHCH₂CH═CHCO₂H CH₃ 197 H CONH₂ CH₃ 198 HCH₂CONH₂ CH₃ 199 H OCH₂CONH₂ CH₃ 200 H CN₄H CH₃ 201 CO₂Et Cl H 202 CO₂HCl H 203 CH₂CO₂Et Cl H 204 CH₂CO₂H Cl H 205 OCH₂CO₂Et Cl H 206 OCH₂CO₂HCl H 207 OCH₂CH₂CH₂PO(OEt)₂ Cl H 208 OCH₂CH₂CH₂PO(OH)₂ Cl H 209OCH₂C₆H₄CO₂Et Cl H 210 OCH₂C₆H₄CO₂H Cl H 211 NHCH₂CO₂Et Cl H 212NHCH₂CO₂H Cl H 213 NHCH₂CH₂CH₂PO(OEt)₂ Cl H 214 NHCH₂CH₂CH₂PO(OH)₂ Cl H215 NHCH₂C₆H₄CO₂Et Cl H 216 NHCH₂C₆H₄CO₂H Cl H 217 NHCOCH₂CH₂CO₂Et Cl H218 NHCOCH₂CH₂CO₂H Cl H 219 NHSO₂CH₃ Cl H 220 NHCH₂CH═CHCO₂Et Cl H 221NHCH₂CH═CHCO₂H Cl H 222 CONH₂ Cl H 223 CH₂CONH₂ Cl H 224 OCH₂CONH₂ Cl H225 CN₄H Cl H 226 Cl CO₂Et H 227 Cl CO₂H H 228 Cl CH₂CO₂Et H 229 ClCH₂CO₂H H 230 Cl OCH₂CO₂Et H 231 Cl OCH₂CO₂H H 232 Cl OCH₂CH₂CH₂PO(OEt)₂H 233 Cl OCH₂CH₂CH₂PO(OH)₂ H 234 Cl OCH₂C₆H₄CO₂Et H 235 Cl OCH₂C₆H₄CO₂HH 236 Cl NHCH₂CO₂Et H 237 Cl NHCH₂CO₂H H 238 Cl NHCH₂CH₂CH₂PO(OEt)₂ H239 Cl NHCH₂CH₂CH₂PO(OH)₂ H 240 Cl NHCH₂C₆H₄CO₂Et H 241 Cl NHCH₂C₆H₄CO₂HH 242 Cl NHCOCH₂CH₂CO₂Et H 243 Cl NHCOCH₂CH₂CO₂H H 244 Cl NHSO₂CH₃ H 245Cl NHCH₂CH═CHCO₂Et H 246 Cl NHCH₂CH═CHCO₂H H 247 Cl CONH₂ H 248 ClCH₂CONH₂ H 249 Cl OCH₂CONH₂ H 250 Cl CN₄H H 251 CO₂Et Cl Cl 252 CO₂H ClCl 253 CH₂CO₂Et Cl Cl 254 CH₂CO₂H Cl Cl 255 OCH₂CO₂Et Cl Cl 256 OCH₂CO₂HCl Cl 257 OCH₂CH₂CH₂PO(OEt)₂ Cl Cl 258 OCH₂CH₂CH₂PO(OH)₂ Cl Cl 259OCH₂C₆H₄CO₂Et Cl Cl 260 OCH₂C₆H₄CO₂H Cl Cl 261 NHCH₂CO₂Et Cl Cl 262NHCH₂CO₂H Cl Cl 263 NHCH₂CH₂CH₂PO(OEt)₂ Cl Cl 264 NHCH₂CH₂CH₂PO(OH)₂ ClCl 265 NHCH₂C₆H₄CO₂Et Cl Cl 266 NHCH₂C₆H₄CO₂H Cl Cl 267 NHCOCH₂CH₂CO₂EtCl Cl 268 NHCOCH₂CH₂CO₂H Cl Cl 269 NHSO₂CH₃ Cl Cl 270 NHCH₂CH═CHCO₂Et ClCl 271 NHCH₂CH═CHCO₂H Cl Cl 272 CONH₂ Cl Cl 273 CH₂CONH₂ Cl Cl 274OCH₂CONH₂ Cl Cl 275 CN₄H Cl Cl 276 Cl CO₂Et Cl 277 Cl CO₂H Cl 278 ClCH₂CO₂Et Cl 279 Cl CH₂CO₂H Cl 280 Cl OCH₂CO₂Et Cl 281 Cl OCH₂CO₂H Cl 282Cl OCH₂CH₂CH₂PO(OEt)₂ Cl 283 Cl OCH₂CH₂CH₂PO(OH)₂ Cl 284 ClOCH₂C₆H₄CO₂Et Cl 285 Cl OCH₂C₆H₄CO₂H Cl 286 Cl NHCH₂CO₂Et Cl 287 ClNHCH₂CO₂H Cl 288 Cl NHCH₂CH₂CH₂PO(OEt)₂ Cl 289 Cl NHCH₂CH₂CH₂PO(OH)₂ Cl290 Cl NHCH₂C₆H₄CO₂Et Cl 291 Cl NHCH₂C₆H₄CO₂H Cl 292 Cl NHCOCH₂CH₂CO₂EtCl 293 Cl NHCOCH₂CH₂CO₂H Cl 294 Cl NHSO₂CH₃ Cl 295 Cl NHCH₂CH═CHCO₂Et Cl296 Cl NHCH₂CH═CHCO₂H Cl 297 Cl CONH₂ Cl 298 Cl CH₂CONH₂ Cl 299 ClOCH₂CONH₂ Cl 300 Cl CN₄H Cl 301 CO₂Et Cl OCH₃ 302 CO₂H Cl OCH₃ 303CH₂CO₂Et Cl OCH₃ 304 CH₂CO₂H Cl OCH₃ 305 OCH₂CO₂Et Cl OCH₃ 306 OCH₂CO₂HCl OCH₃ 307 OCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 308 OCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 309OCH₂C₆H₄CO₂Et Cl OCH₃ 310 OCH₂C₆H₄CO₂H Cl OCH₃ 311 NHCH₂CO₂Et Cl OCH₃312 NHCH₂CO₂H Cl OCH₃ 313 NHCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 314NHCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 315 NHCH₂C₆H₄CO₂Et Cl OCH₃ 316 NHCH₂C₆H₄CO₂HCl OCH₃ 317 NHCOCH₂CH₂CO₂Et Cl OCH₃ 318 NHCOCH₂CH₂CO₂H Cl OCH₃ 319NHSO₂CH₃ Cl OCH₃ 320 NHCH₂CH═CHCO₂Et Cl OCH₃ 321 NHCH₂CH═CHCO₂H Cl OCH₃322 CONH₂ Cl OCH₃ 323 CH₂CONH₂ Cl OCH₃ 324 OCH₂CONH₂ Cl OCH₃ 325 CN₄H ClOCH₃ 326 Cl CO₂Et OCH₃ 327 Cl CO₂H OCH₃ 328 Cl CH₂CO₂Et OCH₃ 329 ClCH₂CO₂H OCH₃ 330 Cl OCH₂CO₂Et OCH₃ 331 Cl OCH₂CO₂H OCH₃ 332 ClOCH₂CH₂CH₂PO(OEt)₂ OCH₃ 333 Cl OCH₂CH₂CH₂PO(OH)₂ OCH₃ 334 ClOCH₂C₆H₄CO₂Et OCH₃ 335 Cl OCH₂C₆H₄CO₂H OCH₃ 336 Cl NHCH₂CO₂Et OCH₃ 337Cl NHCH₂CO₂H OCH₃ 338 Cl NHCH₂CH₂CH₂PO(OEt)₂ OCH₃ 339 ClNHCH₂CH₂CH₂PO(OH)₂ OCH₃ 340 Cl NHCH₂C₆H₄CO₂Et OCH₃ 341 Cl NHCH₂C₆H₄CO₂HOCH₃ 342 Cl NHCOCH₂CH₂CO₂Et OCH₃ 343 Cl NHCOCH₂CH₂CO₂H OCH₃ 344 ClNHSO₂CH₃ OCH₃ 345 Cl NHCH₂CH═CHCO₂Et OCH₃ 346 Cl NHCH₂CH═CHCO₂H OCH₃ 347Cl CONH₂ OCH₃ 348 Cl CH₂CONH₂ OCH₃ 349 Cl OCH₂CONH₂ OCH₃ 350 Cl CN₄HOCH₃ 351 CO₂Et Cl CH₃ 352 CO₂H Cl CH₃ 353 CH₂CO₂Et Cl CH₃ 354 CH₂CO₂H ClCH₃ 355 OCH₂CO₂Et Cl CH₃ 356 OCH₂CO₂H Cl CH₃ 357 OCH₂CH₂CH₂PO(OEt)₂ ClCH₃ 358 OCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 359 OCH₂C₆H₄CO₂Et Cl CH₃ 360OCH₂C₆H₄CO₂H Cl CH₃ 361 NHCH₂CO₂Et Cl CH₃ 362 NHCH₂CO₂H Cl CH₃ 363NHCH₂CH₂CH₂PO(OEt)₂ Cl CH₃ 364 NHCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 365NHCH₂C₆H₄CO₂Et Cl CH₃ 366 NHCH₂C₆H₄CO₂H Cl CH₃ 367 NHCOCH₂CH₂CO₂Et ClCH₃ 368 NHCOCH₂CH₂CO₂H Cl CH₃ 369 NHSO₂CH₃ Cl CH₃ 370 NHCH₂CH═CHCO₂Et ClCH₃ 371 NHCH₂CH═CHCO₂H Cl CH₃ 372 CONH₂ Cl CH₃ 373 CH₂CONH₂ Cl CH₃ 374OCH₂CONH₂ Cl CH₃ 375 CN₄H Cl CH₃ 376 Cl CO₂Et CH₃ 377 Cl CO₂H CH₃ 378 ClCH₂CO₂Et CH₃ 379 Cl CH₂CO₂H CH₃ 380 Cl OCH₂CO₂Et CH₃ 381 Cl OCH₂CO₂H CH₃382 Cl OCH₂CH₂CH₂PO(OEt)₂ CH₃ 383 Cl OCH₂CH₂CH₂PO(OH)₂ CH₃ 384 ClOCH₂C₆H₄CO₂Et CH₃ 385 Cl OCH₂C₆H₄CO₂H CH₃ 386 Cl NHCH₂CO₂Et CH₃ 387 ClNHCH₂CO₂H CH₃ 388 Cl NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 389 Cl NHCH₂CH₂CH₂PO(OH)₂CH₃ 390 Cl NHCH₂C₆H₄CO₂Et CH₃ 391 Cl NHCH₂C₆H₄CO₂H CH₃ 392 ClNHCOCH₂CH₂CO₂Et CH₃ 393 Cl NHCOCH₂CH₂CO₂H CH₃ 394 Cl NHSO₂CH₃ CH₃ 395 ClNHCH₂CH═CHCO₂Et CH₃ 396 Cl NHCH₂CH═CHCO₂H CH₃ 397 Cl CONH₂ CH₃ 398 ClCH₂CONH₂ CH₃ 399 Cl OCH₂CONH₂ CH₃ 400 Cl CN₄H CH₃

TABLE 2b

Ex. # X Y X′ 1 CO₂Et H H 2 CO₂H H H 3 CH₂CO₂Et H H 4 CH₂CO₂H H H 5OCH₂CO₂Et H H 6 OCH₂CO₂H H H 7 OCH₂CH₂CH₂PO(OEt)₂ H H 8OCH₂CH₂CH₂PO(OH)₂ H H 9 OCH₂C₆H₄CO₂Et H H 10 OCH₂C₆H₄CO₂H H H 11NHCH₂CO₂Et H H 12 NHCH₂CO₂H H H 13 NHCH₂CH₂CH₂PO(OEt)₂ H H 14NHCH₂CH₂CH₂PO(OH)₂ H H 15 NHCH₂C₆H₄CO₂H H H 16 NHCH₂C₆H₄CO₂H H H 17NHCOCH₂CH₂CO₂Et H H 18 NHCOCH₂CH₂CO₂H H H 19 NHSO₂CH₃ H H 20NHCH₂CH═CHCO₂Et H H 21 NHCH₂CH═CHCO₂H H H 22 CONH₂ H H 23 CH₂CONH₂ H H24 OCH₂CONH₂ H H 25 CN₄H H H 26 H CO₂Et H 27 H CO₂H H 28 H CH₂CO₂Et H 29H CH₂CO₂H H 30 H OCH₂CO₂Et H 31 H OCH₂CO₂H H 32 H OCH₂CH₂CH₂PO(OEt)₂ H33 H OCH₂CH₂CH₂PO(OH)₂ H 34 H OCH₂C₆H₄CO₂Et H 35 H OCH₂C₆H₄CO₂H H 36 HNHCH₂CO₂Et H 37 H NHCH₂CO₂H H 38 H NHCH₂CH₂CH₂PO(OEt)₂ H 39 HNHCH₂CH₂CH₂PO(OH)₂ H 40 H NHCH₂C₆H₄CO₂Et H 41 H NHCH₂C₆H₄CO₂H H 42 HNHCOCH₂CH₂CO₂Et H 43 H NHCOCH₂CH₂CO₂H H 44 H NHSO₂CH₃ H 45 HNHCH₂CH═CHCO₂Et H 46 H NHCH₂CH═CHCO₂H H 47 H CONH₂ H 48 H CH₂CONH₂ H 49H OCH₂CONH₂ H 50 H CN₄H H 51 CO₂Et H Cl 52 CO₂H H Cl 53 CH₂CO₂Et H Cl 54CH₂CO₂H H Cl 55 OCH₂CO₂Et H Cl 56 OCH₂CO₂H H Cl 57 OCH₂CH₂CH₂PO(OEt)₂ HCl 58 OCH₂CH₂CH₂PO(OH)₂ H Cl 59 OCH₂C₆H₄CO₂Et H Cl 60 OCH₂C₆H₄CO₂H H Cl61 NHCH₂CO₂Et H Cl 62 NHCH₂CO₂H H Cl 63 NHCH₂CH₂CH₂PO(OEt)₂ H Cl 64NHCH₂CH₂CH₂PO(OH)₂ H Cl 65 NHCH₂C₆H₄CO₂Et H Cl 66 NHCH₂C₆H₄CO₂H H Cl 67NHCOCH₂CH₂CO₂Et H Cl 68 NHCOCH₂CH₂CO₂H H Cl 69 NHSO₂CH₃ H Cl 70NHCH₂CH═CHCO₂Et H Cl 71 NHCH₂CH═CHCO₂H H Cl 72 CONH₂ H Cl 73 CH₂CONH₂ HCl 74 OCH₂CONH₂ H Cl 75 CN₄H H Cl 76 H CO₂Et Cl 77 H CO₂H Cl 78 HCH₂CO₂Et Cl 79 H CH₂CO₂H Cl 80 H OCH₂CO₂Et Cl 81 H OCH₂CO₂H Cl 82 HOCH₂CH₂CH₂PO(OEt)₂ Cl 83 H OCH₂CH₂CH₂PO(OH)₂ Cl 84 H OCH₂C₆H₄CO₂Et Cl 85H OCH₂C₆H₄CO₂H Cl 86 H NHCH₂CO₂Et Cl 87 H NHCH₂CO₂H Cl 88 HNHCH₂CH₂CH₂PO(OEt)₂ Cl 89 H NHCH₂CH₂CH₂PO(OH)₂ Cl 90 H NHCH₂C₆H₄CO₂Et Cl91 H NHCH₂C₆H₄CO₂H Cl 92 H NHCOCH₂CH₂CO₂Et Cl 93 H NHCOCH₂CH₂CO₂H Cl 94H NHSO₂CH₃ Cl 95 H NHCH₂CH═CHCO₂Et Cl 96 H NHCH₂CH═CHCOC₂H Cl 97 H CONH₂Cl 98 H CH₂CONH₂ Cl 99 H OCH₂CONH₂ Cl 100 H CN₄H Cl 101 CO₂Et H OCH₃ 102CO₂H H OCH₃ 103 CH₂CO₂Et H OCH₃ 104 CH₂CO₂H H OCH₃ 105 OCH₂CO₂Et H OCH₃106 OCH₂CO₂H H OCH₃ 107 OCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 108 OCH₂CH₂CH₂PO(OH)₂H OCH₃ 109 OCH₂C₆H₄CO₂Et H OCH₃ 110 OCH₂C₆H₄CO₂H H OCH₃ 111 NHCH₂CO₂Et HOCH₃ 112 NHCH₂CO₂H H OCH₃ 113 NHCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 114NHCH₂CH₂CH₂PO(OH)₂ H OCH₃ 115 NHCH₂C₆H₄CO₂Et H OCH₃ 116 NHCH₂C₆H₄CO₂H HOCH₃ 117 NHCOCH₂CH₂CO₂Et H OCH₃ 118 NHCOCH₂CH₂CO₂H H OCH₃ 119 NHSO₂CH₃ HOCH₃ 120 NHCH₂CH═CHCO₂Et H OCH₃ 121 NHCH₂CH═CHCO₂H H OCH₃ 122 CONH₂ HOCH₃ 123 CH₂CONH₂ H OCH₃ 124 OCH₂CONH₂ H OCH₃ 125 CN₄H H OCH₃ 126 HCO₂Et OCH₃ 127 H CO₂H OCH₃ 128 H CH₂CO₂Et OCH₃ 129 H CH₂CO₂H OCH₃ 130 HOCH₂CO₂Et OCH₃ 131 H OCH₂CO₂H OCH₃ 132 H OCH₂CH₂CH₂PO(OEt)₂ OCH₃ 133 HOCH₂CH₂CH₂PO(OH)₂ OCH₃ 134 H OCH₂C₆H₄CO₂Et OCH₃ 135 H OCH₂C₆H₄CO₂H OCH₃136 H NHCH₂CO₂Et OCH₃ 137 H NHCH₂CO₂H OCH₃ 138 H NHCH₂CH₂CH₂PO(OEt)₂OCH₃ 139 H NHCH₂CH₂CH₂PO(OH)₂ OCH₃ 140 H NHCH₂C₆H₄CO₂Et OCH₃ 141 HNHCH₂C₆H₄CO₂H OCH₃ 142 H NHCOCH₂CH₂CO₂Et OCH₃ 143 H NHCOCH₂CH₂CO₂H OCH₃144 H NHSO₂CH₃ OCH₃ 145 H NHCH₂CH═CHCO₂Et OCH₃ 146 H NHCH₂CH═CHCO₂H OCH₃147 H CONH₂ OCH₃ 148 H CH₂CONH₂ OCH₃ 149 H OCH₂CONH₂ OCH₃ 150 H CN₄HOCH₃ 151 CO₂Et H CH₃ 152 CO₂H H CH₃ 153 CH₂CO₂Et H CH₃ 154 CH₂CO₂H H CH₃155 OCH₂CO₂Et H CH₃ 156 OCH₂CO₂H H CH₃ 157 OCH₂CH₂CH₂PO(OEt)₂ H CH₃ 158OCH₂CH₂CH₂PO(OH)₂ H CH₃ 159 OCH₂C₆H₄CO₂Et H CH₃ 160 OCH₂C₆H₄CO₂H H CH₃161 NHCH₂CO₂Et H CH₃ 162 NHCH₂CO₂H H CH₃ 163 NHCH₂CH₂CH₂PO(OEt)₂ H CH₃164 NHCH₂CH₂CH₂PO(OH)₂ H CH₃ 165 NHCH₂C₆H₄CO₂Et H CH₃ 166 NHCH₂C₆H₄CO₂HH CH₃ 167 NHCOCH₂CH₂CO₂Et H CH₃ 168 NHCOCH₂CH₂CO₂H H CH₃ 169 NHSO₂CH₃ HCH₃ 170 NHCH₂CH═CHCO₂Et H CH₃ 171 NHCH₂CH═CHCO₂H H CH₃ 172 CONH₂ H CH₃173 CH₂CONH₂ H CH₃ 174 OCH₂CONH₂ H CH₃ 175 CN₄H H CH₃ 176 H CO₂Et CH₃177 H CO₂H CH₃ 178 H CH₂CO₂Et CH₃ 179 H CH₂CO₂H CH₃ 180 H OCH₂CO₂Et CH₃181 H OCH₂CO₂H CH₃ 182 H OCH₂CH₂CH₂PO(OEt)₂ CH₃ 183 H OCH₂CH₂CH₂PO(OH)₂CH₃ 184 H OCH₂C₆H₄CO₂Et CH₃ 185 H OCH₂C₆H₄CO₂H CH₃ 186 H NHCH₂CO₂Et CH₃187 H NHCH₂CO₂H CH₃ 188 H NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 189 HNHCH₂CH₂CH₂PO(OH)₂ CH₃ 190 H NHCH₂C₆H₄CO₂Et CH₃ 191 H NHCH₂C₆H₄CO₂H CH₃192 H NHCOCH₂CH₂CO₂Et CH₃ 193 H NHCOCH₂CH₂CO₂H CH₃ 194 H NHSO₂CH₃ CH₃195 H NHCH₂CH═CHCO₂Et CH₃ 196 H NHCH₂CH═CHCO₂H CH₃ 197 H CONH₂ CH₃ 198 HCH₂CONH₂ CH₃ 199 H OCH₂CONH₂ CH₃ 200 H CN₄H CH₃ 201 CO₂Et Cl H 202 CO₂HCl H 203 CH₂CO₂Et Cl H 204 CH₂CO₂H Cl H 205 OCH₂CO₂Et Cl H 206 OCH₂CO₂HCl H 207 OCH₂CH₂CH₂PO(OEt)₂ Cl H 208 OCH₂CH₂CH₂PO(OH)₂ Cl H 209OCH₂C₆H₄CO₂Et Cl H 210 OCH₂C₆H₄CO₂H Cl H 211 NHCH₂CO₂Et Cl H 212NHCH₂CO₂H Cl H 213 NHCH₂CH₂CH₂PO(OEt)₂ Cl H 214 NHCH₂CH₂CH₂PO(OH)₂ Cl H215 NHCH₂C₆H₄CO₂Et Cl H 216 NHCH₂C₆H₄CO₂H Cl H 217 NHCOCH₂CH₂CO₂Et Cl H218 NHCOCH₂CH₂CO₂H Cl H 219 NHSO₂CH₃ Cl H 220 NHCH₂CH═CHCO₂Et Cl H 221NHCH₂CH═CHCO₂H Cl H 222 CONH₂ Cl H 223 CH₂CONH₂ Cl H 224 OCH₂CONH₂ Cl H225 CN₄H Cl H 226 Cl CO₂Et H 227 Cl CO₂H H 228 Cl CH₂CO₂Et H 229 ClCH₂CO₂H H 230 Cl OCH₂CO₂Et H 231 Cl OCH₂CO₂H H 232 Cl OCH₂CH₂CH₂PO(OEt)₂H 233 Cl OCH₂CH₂CH₂PO(OH)₂ H 234 Cl OCH₂C₆H₄CO₂Et H 235 Cl OCH₂C₆H₄CO₂HH 236 Cl NHCH₂CO₂Et H 237 Cl NHCH₂CO₂H H 238 Cl NHCH₂CH₂CH₂PO(OEt)₂ H239 Cl NHCH₂CH₂CH₂PO(OH)₂ H 240 Cl NHCH₂C₆H₄CO₂Et H 241 Cl NHCH₂C₆H₄CO₂HH 242 Cl NHCOCH₂CH₂CO₂Et H 243 Cl NHCOCH₂CH₂CO₂H H 244 Cl NHSO₂CH₃ H 245Cl NHCH₂CH═CHCO₂Et H 246 Cl NHCH₂CH═CHCO₂H H 247 Cl CONH₂ H 248 ClCH₂CONH₂ H 249 Cl OCH₂CONH₂ H 250 Cl CN₄H H 251 CO₂Et Cl Cl 252 CO₂H ClCl 253 CH₂CO₂Et Cl Cl 254 CH₂CO₂H Cl Cl 255 OCH₂CO₂Et Cl Cl 256 OCH₂CO₂HCl Cl 257 OCH₂CH₂CH₂PO(OEt)₂ Cl Cl 258 OCH₂CH₂CH₂PO(OH)₂ Cl Cl 259OCH₂C₆H₄CO₂Et Cl Cl 260 OCH₂C₆H₄CO₂H Cl Cl 261 NHCH₂CO₂Et Cl Cl 262NHCH₂CO₂H Cl Cl 263 NHCH₂CH₂CH₂PO(OEt)₂ Cl Cl 264 NHCH₂CH₂CH₂PO(OH)₂ ClCl 265 NHCH₂C₆H₄CO₂Et Cl Cl 266 NHCH₂C₆H₄CO₂H Cl Cl 267 NHCOCH₂CH₂CO₂EtCl Cl 268 NHCOCH₂CH₂CO₂H Cl Cl 269 NHSO₂CH₃ Cl Cl 270 NHCH₂CH═CHCO₂Et ClCl 271 NHCH₂CH═CHCO₂H Cl Cl 272 CONH₂ Cl Cl 273 CH₂CONH₂ Cl Cl 274OCH₂CONH₂ Cl Cl 275 CN₄H Cl Cl 276 Cl CO₂Et Cl 277 Cl CO₂H Cl 278 ClCH₂CO₂Et Cl 279 Cl CH₂CO₂H Cl 280 Cl OCH₂CO₂Et Cl 281 Cl OCH₂CO₂H Cl 282Cl OCH₂CH₂CH₂PO(OEt)₂ Cl 283 Cl OCH₂CH₂CH₂PO(OH)₂ Cl 284 ClOCH₂C₆H₄CO₂Et Cl 285 Cl OCH₂C₆H₄CO₂H Cl 286 Cl NHCH₂CO₂Et Cl 287 ClNHCH₂CO₂H Cl 288 Cl NHCH₂CH₂CH₂PO(OEt)₂ Cl 289 Cl NHCH₂CH₂CH₂PO(OH)₂ Cl290 Cl NHCH₂C₆H₄CO₂Et Cl 291 Cl NHCH₂C₆H₄CO₂H Cl 292 Cl NHCOCH₂CH₂CO₂EtCl 293 Cl NHCOCH₂CH₂CO₂H Cl 294 Cl NHSO₂CH₃ Cl 295 Cl NHCH₂CH═CHCO₂Et Cl296 Cl NHCH₂CH═CHCO₂H Cl 297 Cl CONH₂ Cl 298 Cl CH₂CONH₂ Cl 299 ClOCH₂CONH₂ Cl 300 Cl CN₄H Cl 301 CO₂Et Cl OCH₃ 302 CO₂H Cl OCH₃ 303CH₂CO₂Et Cl OCH₃ 304 CH₂CO₂H Cl OCH₃ 305 OCH₂CO₂Et Cl OCH₃ 306 OCH₂CO₂HCl OCH₃ 307 OCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 308 OCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 309OCH₂C₆H₄CO₂Et Cl OCH₃ 310 OCH₂C₆H₄CO₂H Cl OCH₃ 311 NHCH₂CO₂Et Cl OCH₃312 NHCH₂CO₂H Cl OCH₃ 313 NHCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 314NHCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 315 NHCH₂C₆H₄CO₂Et Cl OCH₃ 316 NHCH₂C₆H₄CO₂HCl OCH₃ 317 NHCOCH₂CH₂CO₂Et Cl OCH₃ 318 NHCOCH₂CH₂CO₂H Cl OCH₃ 319NHSO₂CH₃ Cl OCH₃ 320 NHCH₂CH═CHCO₂Et Cl OCH₃ 321 NHCH₂CH═CHCO₂H Cl OCH₃322 CONH₂ Cl OCH₃ 323 CH₂CONH₂ Cl OCH₃ 324 OCH₂CONH₂ Cl OCH₃ 325 CN₄H ClOCH₃ 326 Cl CO₂Et OCH₃ 327 Cl CO₂H OCH₃ 328 Cl CH₂CO₂Et OCH₃ 329 ClCH₂CO₂H OCH₃ 330 Cl OCH₂CO₂Et OCH₃ 331 Cl OCH₂CO₂H OCH₃ 332 ClOCH₂CH₂CH₂PO(OEt)₂ OCH₃ 333 Cl OCH₂CH₂CH₂PO(OH)₂ OCH₃ 334 ClOCH₂C₆H₄CO₂Et OCH₃ 335 Cl OCH₂C₆H₄CO₂H OCH₃ 336 Cl NHCH₂CO₂Et OCH₃ 337Cl NHCH₂CO₂H OCH₃ 338 Cl NHCH₂CH₂CH₂PO(OEt)₂ OCH₃ 339 ClNHCH₂CH₂CH₂PO(OH)₂ OCH₃ 340 Cl NHCH₂C₆H₄CO₂Et OCH₃ 341 Cl NHCH₂C₆H₄CO₂HOCH₃ 342 Cl NHCOCH₂CH₂CO₂Et OCH₃ 343 Cl NHCOCH₂CH₂CO₂H OCH₃ 344 ClNHSO₂CH₃ OCH₃ 345 Cl NHCH₂CH═CHCO₂Et OCH₃ 346 Cl NHCH₂CH═CHCO₂H OCH₃ 347Cl CONH₂ OCH₃ 348 Cl CH₂CONH₂ OCH₃ 349 Cl OCH₂CONH₂ OCH₃ 350 Cl CN₄HOCH₃ 351 CO₂Et Cl CH₃ 352 CO₂H Cl CH₃ 353 CH₂CO₂Et Cl CH₃ 354 CH₂CO₂H ClCH₃ 355 OCH₂CO₂Et Cl CH₃ 356 OCH₂CO₂H Cl CH₃ 357 OCH₂CH₂CH₂PO(OEt)₂ ClCH₃ 358 OCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 359 OCH₂C₆H₄CO₂Et Cl CH₃ 360OCH₂C₆H₄CO₂H Cl CH₃ 361 NHCH₂CO₂Et Cl CH₃ 362 NHCH₂CO₂H Cl CH₃ 363NHCH₂CH₂CH₂PO(OEt)₂ Cl CH₃ 364 NHCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 365NHCH₂C₆H₄CO₂Et Cl CH₃ 366 NHCH₂C₆H₄CO₂H Cl CH₃ 367 NHCOCH₂CH₂CO₂Et ClCH₃ 368 NHCOCH₂CH₂CO₂H Cl CH₃ 369 NHSO₂CH₃ Cl CH₃ 370 NHCH₂CH═CHCO₂Et ClCH₃ 371 NHCH₂CH═CHCO₂H Cl CH₃ 372 CONH₂ Cl CH₃ 373 CH₂CONH₂ Cl CH₃ 374OCH₂CONH₂ Cl CH₃ 375 CN₄H Cl CH₃ 376 Cl CO₂Et CH₃ 377 Cl CO₂H CH₃ 378 ClCH₂CO₂Et CH₃ 379 Cl CH₂CO₂H CH₃ 380 Cl OCH₂CO₂Et CH₃ 381 Cl OCH₂CO₂H CH₃382 Cl OCH₂CH₂CH₂PO(OEt)₂ CH₃ 383 Cl OCH₂CH₂CH₂PO(OH)₂ CH₃ 384 ClOCH₂C₆H₄CO₂Et CH₃ 385 Cl OCH₂C₆H₄CO₂H CH₃ 386 Cl NHCH₂CO₂Et CH₃ 387 ClNHCH₂CO₂H CH₃ 388 Cl NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 389 Cl NHCH₂CH₂CH₂PO(OH)₂CH₃ 390 Cl NHCH₂C₆H₄CO₂Et CH₃ 391 Cl NHCH₂C₆H₄CO₂H CH₃ 392 ClNHCOCH₂CH₂CO₂Et CH₃ 393 Cl NHCOCH₂CH₂CO₂H CH₃ 394 Cl NHSO₂CH₃ CH₃ 395 ClNHCH₂CH═CHCO₂Et CH₃ 396 Cl NHCH₂CH═CHCO₂H CH₃ 397 Cl CONH₂ CH₃ 398 ClCH₂CONH₂ CH₃ 399 Cl OCH₂CONH₂ CH₃ 400 Cl CN₄H CH₃

TABLE 3a

Ex. # X′ Y′ X 1 CO₂Et H H 2 CO₂H H H 3 CH₂CO₂Et H H 4 CH₂CO₂H H H 5OCH₂CO₂Et H H 6 OCH₂CO₂H H H 7 OCH₂CH₂CH₂PO(OEt)₂ H H 8OCH₂CH₂CH₂PO(OH)₂ H H 9 OCH₂C₆H₄CO₂Et H H 10 OCH₂C₆H₄CO₂H H H 11NHCH₂CO₂Et H H 12 NHCH₂CO₂H H H 13 NHCH₂CH₂CH₂PO(OEt)₂ H H 14NHCH₂CH₂CH₂PO(OH)₂ H H 15 NHCH₂C₆H₄CO₂Et H H 16 NHCH₂C₆H₄CO₂H H H 17NHCOCH₂CH₂CO₂Et H H 18 NHCOCH₂CH₂CO₂H H H 19 NHSO₂CH₃ H H 20NHCH₂CH═CHCO₂Et H H 21 NHCH₂CH═CHCO₂H H H 22 CONH₂ H H 23 CH₂CONH₂ H H24 OCH₂CONH₂ H H 25 CN₄H H H 26 H CO₂Et H 27 H CO₂H H 28 H CH₂CO₂Et H 29H CH₂CO₂H H 30 H OCH₂CO₂Et H 31 H OCH₂CO₂H H 32 H OCH₂CH₂CH₂PO(OEt)₂ H33 H OCH₂CH₂CH₂PO(OH)₂ H 34 H OCH₂C₆H₄CO₂Et H 35 H OCH₂C₆H₄CO₂H H 36 HNHCH₂CO₂Et H 37 H NHCH₂CO₂H H 38 H NHCH₂CH₂CH₂PO(OEt)₂ H 39 HNHCH₂CH₂CH₂PO(OH)₂ H 40 H NHCH₂C₆H₄CO₂Et H 41 H NHCH₂C₆H₄CO₂H H 42 HNHCOCH₂CH₂CO₂Et H 43 H NHCOCH₂CH₂CO₂H H 44 H NHSO₂CH₃ H 45 HNHCH₂CH═CHCO₂Et H 46 H NHCH₂CH═CHCO₂H H 47 H CONH₂ H 48 H CH₂CONH₂ H 49H OCH₂CONH₂ H 50 H CN₄H H 51 CO₂Et H Cl 52 CO₂H H Cl 53 CH₂CO₂Et H Cl 54CH₂CO₂H H Cl 55 OCH₂CO₂Et H Cl 56 OCH₂CO₂H H Cl 57 OCH₂CH₂CH₂PO(OEt)₂ HCl 58 OCH₂CH₂CH₂PO(OH)₂ H Cl 59 OCH₂C₆H₄CO₂Et H Cl 60 OCH₂C₆H₄CO₂H H Cl61 NHCH₂CO₂Et H Cl 62 NHCH₂CO₂H H Cl 63 NHCH₂CH₂CH₂PO(OEt)₂ H Cl 64NHCH₂CH₂CH₂PO(OH)₂ H Cl 65 NHCH₂C₆H₄CO₂Et H Cl 66 NHCH₂C₆H₄CO₂H H Cl 67NHCOCH₂CH₂CO₂Et H Cl 68 NHCOCH₂CH₂CO₂H H Cl 69 NHSO₂CH₃ H Cl 70NHCH₂CH═CHCO₂Et H Cl 71 NHCH₂CH═CHCO₂H H Cl 72 CONH₂ H Cl 73 CH₂CONH₂ HCl 74 OCH₂CONH₂ H Cl 75 CN₄H H Cl 76 H CO₂Et Cl 77 H CO₂H Cl 78 HCH₂CO₂Et Cl 79 H CH₂CO₂H Cl 80 H OCH₂CO₂Et Cl 81 H OCH₂CO₂H Cl 82 HOCH₂CH₂CH₂PO(OEt)₂ Cl 83 H OCH₂CH₂CH₂PO(OH)₂ Cl 84 H OCH₂C₆H₄CO₂Et Cl 85H OCH₂C₆H₄CO₂H Cl 86 H NHCH₂CO₂Et Cl 87 H NHCH₂CO₂H Cl 88 HNHCH₂CH₂CH₂PO(OEt)₂ Cl 89 H NHCH₂CH₂CH₂PO(OH)₂ Cl 90 H NHCH₂C₆H₄CO₂Et Cl91 H NHCH₂C₆H₄CO₂H Cl 92 H NHCOCH₂CH₂CO₂Et Cl 93 H NHCOCH₂CH₂CO₂H Cl 94H NHSO₂CH₃ Cl 95 H NHCH₂CH═CHCO₂Et Cl 96 H NHCH₂CH═CHCO₂H Cl 97 H CONH₂Cl 98 H CH₂CONH₂ Cl 99 H OCH₂CONH₂ Cl 100 H CN₄H Cl 101 CO₂Et H OCH₃ 102CO₂H H OCH₃ 103 CH₂CO₂Et H OCH₃ 104 CH₂CO₂H H OCH₃ 105 OCH₂CO₂Et H OCH₃106 OCH₂CO₂H H OCH₃ 107 OCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 108 OCH₂CH₂CH₂PO(OH)₂H OCH₃ 109 OCH₂C₆H₄CO₂Et H OCH₃ 110 OCH₂C₆H₄CO₂H H OCH₃ 111 NHCH₂CO₂Et HOCH₃ 112 NHCH₂CO₂H H OCH₃ 113 NHCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 114NHCH₂CH₂CH₂PO(OH)₂ H OCH₃ 115 NHCH₂C₆H₄CO₂Et H OCH₃ 116 NHCH₂C₆H₄CO₂H HOCH₃ 117 NHCOCH₂CH₂CO₂Et H OCH₃ 118 NHCOCH₂CH₂CO₂H H OCH₃ 119 NHSO₂CH₃ HOCH₃ 120 NHCH₂CH═CHCO₂Et H OCH₃ 121 NHCH₂CH═CHCO₂H H OCH₃ 122 CONH₂ HOCH₃ 123 CH₂CONH₂ H OCH₃ 124 OCH₂CONH₂ H OCH₃ 125 CN₄H H OCH₃ 126 HCO₂Et OCH₃ 127 H CO₂H OCH₃ 128 H CH₂CO₂Et OCH₃ 129 H CH₂CO₂H OCH₃ 130 HOCH₂CO₂Et OCH₃ 131 H OCH₂CO₂H OCH₃ 132 H OCH₂CH₂CH₂PO(OEt)₂ OCH₃ 133 HOCH₂CH₂CH₂PO(OH)₂ OCH₃ 134 H OCH₂C₆H₄CO₂Et OCH₃ 135 H OCH₂C₆H₄CO₂H OCH₃136 H NHCH₂CO₂Et OCH₃ 137 H NHCH₂CO₂H OCH₃ 138 H NHCH₂CH₂CH₂PO(OEt)₂OCH₃ 139 H NHCH₂CH₂CH₂PO(OH)₂ OCH₃ 140 H NHCH₂C₆H₄CO₂Et OCH₃ 141 HNHCH₂C₆H₄CO₂H OCH₃ 142 H NHCOCH₂CH₂CO₂Et OCH₃ 143 H NHCOCH₂CH₂CO₂H OCH₃144 H NHSO₂CH₃ OCH₃ 145 H NHCH₂CH═CHCO₂Et OCH₃ 146 H NHCH₂CH═CHCO₂H OCH₃147 H CONH₂ OCH₃ 148 H CH₂CONH₂ OCH₃ 149 H OCH₂CONH₂ OCH₃ 150 H CN₄HOCH₃ 151 CO₂Et H CH₃ 152 CO₂H H CH₃ 153 CH₂CO₂Et H CH₃ 154 CH₂CO₂H H CH₃155 OCH₂CO₂Et H CH₃ 156 OCH₂CO₂H H CH₃ 157 OCH₂CH₂CH₂PO(OEt)₂ H CH₃ 158OCH₂CH₂CH₂PO(OH)₂ H CH₃ 159 OCH₂C₆H₄CO₂Et H CH₃ 160 OCH₂C₆H₄CO₂H H CH₃161 NHCH₂CO₂Et H CH₃ 162 NHCH₂CO₂H H CH₃ 163 NHCH₂CH₂CH₂PO(OEt)₂ H CH₃164 NHCH₂CH₂CH₂PO(OH)₂ H CH₃ 165 NHCH₂C₆H₄CO₂Et H CH₃ 166 NHCH₂C₆H₄CO₂HH CH₃ 167 NHCOCH₂CH₂CO₂Et H CH₃ 168 NHCOCH₂CH₂CO₂H H CH₃ 169 NHSO₂CH₃ HCH₃ 170 NHCH₂CH═CHCO₂Et H CH₃ 171 NHCH₂CH═CHCO₂H H CH₃ 172 CONH₂ H CH₃173 CH₂CONH₂ H CH₃ 174 OCH₂CONH₂ H CH₃ 175 CN₄H H CH₃ 176 H CO₂Et CH₃177 H CO₂H CH₃ 178 H CH₂CO₂Et CH₃ 179 H CH₂CO₂H CH₃ 180 H OCH₂CO₂Et CH₃181 H OCH₂CO₂H CH₃ 182 H OCH₂CH₂CH₂PO(OEt)₂ CH₃ 183 H OCH₂CH₂CH₂PO(OH)₂CH₃ 184 H OCH₂C₆H₄CO₂Et CH₃ 185 H OCH₂C₆H₄CO₂H CH₃ 186 H NHCH₂CO₂Et CH₃187 H NHCH₂CO₂H CH₃ 188 H NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 189 HNHCH₂CH₂CH₂PO(OH)₂ CH₃ 190 H NHCH₂C₆H₄CO₂Et CH₃ 191 H NHCH₂C₆H₄CO₂H CH₃192 H NHCOCH₂CH₂CO₂Et CH₃ 193 H NHCOCH₂CH₂CO₂H CH₃ 194 H NHSO₂CH₃ CH₃195 H NHCH₂CH═CHCO₂Et CH₃ 196 H NHCH₂CH═CHCO₂H CH₃ 197 H CONH₂ CH₃ 198 HCH₂CONH₂ CH₃ 199 H OCH₂CONH₂ CH₃ 200 H CN₄H CH₃ 201 CO₂Et Cl H 202 CO₂HCl H 203 CH₂CO₂Et Cl H 204 CH₂CO₂H Cl H 205 OCH₂CO₂Et Cl H 206 OCH₂CO₂HCl H 207 OCH₂CH₂CH₂PO(OEt)₂ Cl H 208 OCH₂CH₂CH₂PO(OH)₂ Cl H 209OCH₂C₆H₄CO₂Et Cl H 210 OCH₂C₆H₄CO₂H Cl H 211 NHCH₂CO₂Et Cl H 212NHCH₂CO₂H Cl H 213 NHCH₂CH₂CH₂PO(OEt)₂ Cl H 214 NHCH₂CH₂CH₂PO(OH)₂ Cl H215 NHCH₂C₆H₄CO₂Et Cl H 216 NHCH₂C₆H₄CO₂H Cl H 217 NHCOCH₂CH₂CO₂Et Cl H218 NHCOCH₂CH₂CO₂H Cl H 219 NHSO₂CH₃ Cl H 220 NHCH₂CH═CHCO₂Et Cl H 221NHCH₂CH═CHCO₂H Cl H 222 CONH₂ Cl H 223 CH₂CONH₂ Cl H 224 OCH₂CONH₂ Cl H225 CN₄H Cl H 226 Cl CO₂Et H 227 Cl CO₂H H 228 Cl CH₂CO₂Et H 229 ClCH₂CO₂H H 230 Cl OCH₂CO₂Et H 231 Cl OCH₂CO₂H H 232 Cl OCH₂CH₂CH₂PO(OEt)₂H 233 Cl OCH₂CH₂CH₂PO(OH)₂ H 234 Cl OCH₂C₆H₄CO₂Et H 235 Cl OCH₂C₆H₄CO₂HH 236 Cl NHCH₂CO₂Et H 237 Cl NHCH₂CO₂H H 238 Cl NHCH₂CH₂CH₂PO(OEt)₂ H239 Cl NHCH₂CH₂CH₂PO(OH)₂ H 240 Cl NHCH₂C₆H₄CO₂Et H 241 Cl NHCH₂C₆H₄CO₂HH 242 Cl NHCOCH₂CH₂CO₂Et H 243 Cl NHCOCH₂CH₂CO₂H H 244 Cl NHSO₂CH₃ H 245Cl NHCH₂CH═CHOC₂Et H 246 Cl NHCH₂CH═CHCO₂H H 247 Cl CONH₂ H 248 ClCH₂CONH₂ H 249 Cl OCH₂CONH₂ H 250 Cl CN₄H H 251 CO₂Et Cl Cl 252 CO₂H ClCl 253 CH₂CO₂Et Cl Cl 254 CH₂CO₂H Cl Cl 255 OCH₂CO₂Et Cl Cl 256 OCH₂CO₂HCl Cl 257 OCH₂CH₂CH₂PO(OEt)₂ Cl Cl 258 OCH₂CH₂CH₂PO(OH)₂ Cl Cl 259OCH₂C₆H₄CO₂Et Cl Cl 260 OCH₂C₆H₄CO₂H Cl Cl 261 NHCH₂CO₂Et Cl Cl 262NHCH₂CO₂H Cl Cl 263 NHCH₂CH₂CH₂PO(OEt)₂ Cl Cl 264 NHCH₂CH₂CH₂PO(OH)₂ ClCl 265 NHCH₂C₆H₄CO₂Et Cl Cl 266 NHCH₂C₆H₄CO₂H Cl Cl 267 NHCOCH₂CH₂CO₂EtCl Cl 268 NHCOCH₂CH₂CO₂H Cl Cl 269 NHSO₂CH₃ Cl Cl 270 NHCH₂CH═CHCO₂Et ClCl 271 NHCH₂CH═CHCO₂H Cl Cl 272 CONH₂ Cl Cl 273 CH₂CONH₂ Cl Cl 274OCH₂CONH₂ Cl Cl 275 CN₄H Cl Cl 276 Cl CO₂Et Cl 277 Cl CO₂H Cl 278 ClCH₂CO₂Et Cl 279 Cl CH₂CO₂H Cl 280 Cl OCH₂CO₂Et Cl 281 Cl OCH₂CO₂H Cl 282Cl OCH₂CH₂CH₂PO(OEt)₂ Cl 283 Cl OCH₂CH₂CH₂PO(OH)₂ Cl 284 ClOCH₂C₆H₄CO₂Et Cl 285 Cl OCH₂C₆H₄CO₂H Cl 286 Cl NHCH₂CO₂Et Cl 287 ClNHCH₂CO₂H Cl 288 Cl NHCH₂CH₂CH₂PO(OEt)₂ Cl 289 Cl NHCH₂CH₂CH₂PO(OH)₂ Cl290 Cl NHCH₂C₆H₄CO₂Et Cl 291 Cl NHCH₂C₆H₄CO₂H Cl 292 Cl NHCOCH₂CH₂CO₂EtCl 293 Cl NHCOCH₂CH₂CO₂H Cl 294 Cl NHSO₂CH₃ Cl 295 Cl NHCH₂CH═CHCO₂Et Cl296 Cl NHCH₂CH═CHCO₂H Cl 297 Cl CONH₂ Cl 298 Cl CH₂CONH₂ Cl 299 ClOCH₂CONH₂ Cl 300 Cl CN₄H Cl 301 CO₂Et Cl OCH₃ 302 CO₂H Cl OCH₃ 303CH₂CO₂Et Cl OCH₃ 304 CH₂CO₂H Cl OCH₃ 305 OCH₂CO₂Et Cl OCH₃ 306 OCH₂CO₂HCl OCH₃ 307 OCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 308 OCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 309OCH₂C₆H₄CO₂Et Cl OCH₃ 310 OCH₂C₆H₄CO₂H Cl OCH₃ 311 NHCH₂CO₂Et Cl OCH₃312 NHCH₂CO₂H Cl OCH₃ 313 NHCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 314NHCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 315 NHCH₂C₆H₄CO₂Et Cl OCH₃ 316 NHCH₂C₆H₄CO₂HCl OCH₃ 317 NHCOCH₂CH₂CO₂Et Cl OCH₃ 318 NHCOCH₂CH₂CO₂H Cl OCH₃ 319NHSO₂CH₃ Cl OCH₃ 320 NHCH₂CH═CHCO₂Et Cl OCH₃ 321 NHCH₂CH═CHCO₂H Cl OCH₃322 CONH₂ Cl OCH₃ 323 CH₂CONH₂ Cl OCH₃ 324 OCH₂CONH₂ Cl OCH₃ 325 CN₄H ClOCH₃ 326 Cl CO₂Et OCH₃ 327 Cl CO₂H OCH₃ 328 Cl CH₂CO₂Et OCH₃ 329 ClCH₂CO₂H OCH₃ 330 Cl OCH₂CO₂Et OCH₃ 331 Cl OCH₂CO₂H OCH₃ 332 ClOCH₂CH₂CH₂PO(OEt)₂ OCH₃ 333 Cl OCH₂CH₂CH₂PO(OH)₂ OCH₃ 334 ClOCH₂C₆H₄CO₂Et OCH₃ 335 Cl OCH₂C₆H₄CO₂H OCH₃ 336 Cl NHCH₂CO₂Et OCH₃ 337Cl NHCH₂CO₂H OCH₃ 338 Cl NHCH₂CH₂CH₂PO(OEt)₂ OCH₃ 339 ClNHCH₂CH₂CH₂PO(OH)₂ OCH₃ 340 Cl NHCH₂C₆H₄CO₂Et OCH₃ 341 Cl NHCH₂C₆H₄CO₂HOCH₃ 342 Cl NHCOCH₂CH₂CO₂Et OCH₃ 343 Cl NHCOCH₂CH₂CO₂H OCH₃ 344 ClNHSO₂CH₃ OCH₃ 345 Cl NHCH₂CH═CHCO₂Et OCH₃ 346 Cl NHCH₂CH═CHCO₂H OCH₃ 347Cl CONH₂ OCH₃ 348 Cl CH₂CONH₂ OCH₃ 349 Cl OCH₂CONH₂ OCH₃ 350 Cl CN₄HOCH₃ 351 CO₂Et Cl CH₃ 352 CO₂H Cl CH₃ 353 CH₂CO₂Et Cl CH₃ 354 CH₂CO₂H ClCH₃ 355 OCH₂CO₂Et Cl CH₃ 356 OCH₂CO₂H Cl CH₃ 357 OCH₂CH₂CH₂PO(OEt)₂ ClCH₃ 358 OCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 359 OCH₂C₆H₄CO₂Et Cl CH₃ 360OCH₂C₆H₄CO₂H Cl CH₃ 361 NHCH₂CO₂Et Cl CH₃ 362 NHCH₂CO₂H Cl CH₃ 363NHCH₂CH₂CH₂PO(OEt)₂ Cl CH₃ 364 NHCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 365NHCH₂C₆H₄CO₂Et Cl CH₃ 366 NHCH₂C₆H₄CO₂H Cl CH₃ 367 NHCOCH₂CH₂CO₂Et ClCH₃ 368 NHCOCH₂CH₂CO₂H Cl CH₃ 369 NHSO₂CH₃ Cl CH₃ 370 NHCH₂CH═CHCO₂Et ClCH₃ 371 NHCH₂CH═CHCO₂H Cl CH₃ 372 CONH₂ Cl CH₃ 373 CH₂CONH₂ Cl CH₃ 374OCH₂CONH₂ Cl CH₃ 375 CN₄H Cl CH₃ 376 Cl CO₂Et CH₃ 377 Cl CO₂H CH₃ 378 ClCH₂CO₂Et CH₃ 379 Cl CH₂CO₂H CH₃ 380 Cl OCH₂CO₂Et CH₃ 381 Cl OCH₂CO₂H CH₃382 Cl OCH₂CH₂CH₂PO(OEt)₂ CH₃ 383 Cl OCH₂CH₂CH₂PO(OH)₂ CH₃ 384 ClOCH₂C₆H₄CO₂Et CH₃ 385 Cl OCH₂C₆H₄CO₂H CH₃ 386 Cl NHCH₂CO₂Et CH₃ 387 ClNHCH₂CO₂H CH₃ 388 Cl NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 389 Cl NHCH₂CH₂CH₂PO(OH)₂CH₃ 390 Cl NHCH₂C₆H₄CO₂Et CH₃ 391 Cl NHCH₂C₆H₄CO₂H CH₃ 392 ClNHCOCH₂CH₂CO₂Et CH₃ 393 Cl NHCOCH₂CH₂CO₂H CH₃ 394 Cl NHSO₂CH₃ CH₃ 395 ClNHCH₂CH═CHCO₂Et CH₃ 396 Cl NHCH₂CH═CHCO₂H CH₃ 397 Cl CONH₂ CH₃ 398 ClCH₂CONH₂ CH₃ 399 Cl OCH₂CONH₂ CH₃ 400 Cl CN₄H CH₃

TABLE 3b

Ex. # X′ Y′ X 1 CO₂Et H H 2 CO₂H H H 3 CH₂CO₂Et H H 4 CH₂CO₂H H H 5OCH₂CO₂Et H H 6 OCH₂CO₂H H H 7 OCH₂CH₂CH₂PO(OEt)₂ H H 8OCH₂CH₂CH₂PO(OH)₂ H H 9 OCH₂C₆H₄CO₂Et H H 10 OCH₂C₆H₄CO₂H H H 11NHCH₂CO₂Et H H 12 NHCH₂CO₂H H H 13 NHCH₂CH₂CH₂PO(OEt)₂ H H 14NHCH₂CH₂CH₂PO(OH)₂ H H 15 NHCH₂C₆H₄CO₂Et H H 16 NHCH₂C₆H₄CO₂H H H 17NHCOCH₂CH₂CO₂Et H H 18 NHCOCH₂CH₂CO₂H H H 19 NHSO₂CH₃ H H 20NHCH₂CH═CHCO₂Et H H 21 NHCH₂CH═CHCO₂H H H 22 CONH₂ H H 23 CH₂CONH₂ H H24 OCH₂CONH₂ H H 25 CN₄H H H 26 H CO₂Et H 27 H CO₂H H 28 H CH₂CO₂Et H 29H CH₂CO₂H H 30 H OCH₂CO₂Et H 31 H OCH₂CO₂H H 32 H OCH₂CH₂CH₂PO(OEt)₂ H33 H OCH₂CH₂CH₂PO(OH)₂ H 34 H OCH₂C₆H₄CO₂Et H 35 H OCH₂C₆H₄CO₂H H 36 HNHCH₂CO₂Et H 37 H NHCH₂CO₂H H 38 H NHCH₂CH₂CH₂PO(OEt)₂ H 39 HNHCH₂CH₂CH₂PO(OH)₂ H 40 H NHCH₂C₆H₄CO₂Et H 41 H NHCH₂C₆H₄CO₂H H 42 HNHCOCH₂CH₂CO₂Et H 43 H NHCOCH₂CH₂CO₂H H 44 H NHSO₂CH₃ H 45 HNHCH₂CH═CHCO₂Et H 46 H NHCH₂CH═CHCO₂H H 47 H CONH₂ H 48 H CH₂CONH₂ H 49H OCH₂CONH₂ H 50 H CN₄H H 51 CO₂Et H Cl 52 CO₂H H Cl 53 CH₂CO₂Et H Cl 54CH₂CO₂H H Cl 55 OCH₂CO₂Et H Cl 56 OCH₂CO₂H H Cl 57 OCH₂CH₂CH₂PO(OEt)₂ HCl 58 OCH₂CH₂CH₂PO(OH)₂ H Cl 59 OCH₂C₆H₄CO₂Et H Cl 60 OCH₂C₆H₄CO₂H H Cl61 NHCH₂CO₂Et H Cl 62 NHCH₂CO₂H H Cl 63 NHCH₂CH₂CH₂PO(OEt)₂ H Cl 64NHCH₂CH₂CH₂PO(OH)₂ H Cl 65 NHCH₂C₆H₄CO₂Et H Cl 66 NHCH₂C₆H₄CO₂H H Cl 67NHCOCH₂CH₂CO₂Et H Cl 68 NHCOCH₂CH₂CO₂H H Cl 69 NHSO₂CH₃ H Cl 70NHCH₂CH═CHCO₂Et H Cl 71 NHCH₂CH═CHCO₂H H Cl 72 CONH₂ H Cl 73 CH₂CONH₂ HCl 74 OCH₂CONH₂ H Cl 75 CN₄H H Cl 76 H CO₂Et Cl 77 H CO₂H Cl 78 HCH₂CO₂Et Cl 79 H CH₂CO₂H Cl 80 H OCH₂CO₂Et Cl 81 H OCH₂CO₂H Cl 82 HOCH₂CH₂CH₂PO(OEt)₂ Cl 83 H OCH₂CH₂CH₂PO(OH)₂ Cl 84 H OCH₂C₆H₄CO₂Et Cl 85H OCH₂C₆H₄CO₂H Cl 86 H NHCH₂CO₂Et Cl 87 H NHCH₂CO₂H Cl 88 HNHCH₂CH₂CH₂PO(OEt)₂ Cl 89 H NHCH₂CH₂CH₂PO(OH)₂ Cl 90 H NHCH₂C₆H₄CO₂Et Cl91 H NHCH₂C₆H₄CO₂H Cl 92 H NHCOCH₂CH₂CO₂Et Cl 93 H NHCOCH₂CH₂CO₂H Cl 94H NHSO₂CH₃ Cl 95 H NHCH₂CH═CHCO₂Et Cl 96 H NHCH₂CH═CHCO₂H Cl 97 H CONH₂Cl 98 H CH₂CONH₂ Cl 99 H OCH₂CONH₂ Cl 100 H CN₄H Cl 101 CO₂Et H OCH₃ 102CO₂H H OCH₃ 103 CH₂CO₂Et H OCH₃ 104 CH₂CO₂H H OCH₃ 105 OCH₂CO₂Et H OCH₃106 OCH₂CO₂H H OCH₃ 107 OCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 108 OCH₂CH₂CH₂PO(OH)₂H OCH₃ 109 OCH₂C₆H₄CO₂Et H OCH₃ 110 OCH₂C₆H₄CO₂H H OCH₃ 111 NHCH₂CO₂Et HOCH₃ 112 NHCH₂CO₂H H OCH₃ 113 NHCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 114NHCH₂CH₂CH₂PO(OH)₂ H OCH₃ 115 NHCH₂C₆H₄CO₂Et H OCH₃ 116 NHCH₂C₆H₄CO₂H HOCH₃ 117 NHCOCH₂CH₂CO₂Et H OCH₃ 118 NHCOCH₂CH₂CO₂H H OCH₃ 119 NHSO₂CH₃ HOCH₃ 120 NHCH₂CH═CHCO₂Et H OCH₃ 121 NHCH₂CH═CHCO₂H H OCH₃ 122 CONH₂ HOCH₃ 123 CH₂CONH₂ H OCH₃ 124 OCH₂CONH₂ H OCH₃ 125 CN₄H H OCH₃ 126 HCO₂Et OCH₃ 127 H CO₂H OCH₃ 128 H CH₂CO₂Et OCH₃ 129 H CH₂CO₂H OCH₃ 130 HOCH₂CO₂Et OCH₃ 131 H OCH₂CO₂H OCH₃ 132 H OCH₂CH₂CH₂PO(OEt)₂ OCH₃ 133 HOCH₂CH₂CH₂PO(OH)₂ OCH₃ 134 H OCH₂C₆H₄CO₂Et OCH₃ 135 H OCH₂C₆H₄CO₂H OCH₃136 H NHCH₂CO₂Et OCH₃ 137 H NHCH₂CO₂H OCH₃ 138 H NHCH₂CH₂CH₂PO(OEt)₂OCH₃ 139 H NHCH₂CH₂CH₂PO(OH)₂ OCH₃ 140 H NHCH₂C₆H₄CO₂Et OCH₃ 141 HNHCH₂C₆H₄CO₂H OCH₃ 142 H NHCOCH₂CH₂CO₂Et OCH₃ 143 H NHCOCH₂CH₂CO₂H OCH₃144 H NHSO₂CH₃ OCH₃ 145 H NHCH₂CH═CHCO₂Et OCH₃ 146 H NHCH₂CH═CHCO₂H OCH₃147 H CONH₂ OCH₃ 148 H CH₂CONH₂ OCH₃ 149 H OCH₂CONH₂ OCH₃ 150 H CN₄HOCH₃ 151 CO₂Et H CH₃ 152 CO₂H H CH₃ 153 CH₂CO₂Et H CH₃ 154 CH₂CO₂H H CH₃155 OCH₂CO₂Et H CH₃ 156 OCH₂CO₂H H CH₃ 157 OCH₂CH₂CH₂PO(OEt)₂ H CH₃ 158OCH₂CH₂CH₂PO(OH)₂ H CH₃ 159 OCH₂C₆H₄CO₂Et H CH₃ 160 OCH₂C₆H₄CO₂H H CH₃161 NHCH₂CO₂Et H CH₃ 162 NHCH₂CO₂H H CH₃ 163 NHCH₂CH₂CH₂PO(OEt)₂ H CH₃164 NHCH₂CH₂CH₂PO(OH)₂ H CH₃ 165 NHCH₂C₆H₄CO₂Et H CH₃ 166 NHCH₂C₆H₄CO₂HH CH₃ 167 NHCOCH₂CH₂CO₂Et H CH₃ 168 NHCOCH₂CH₂CO₂H H CH₃ 169 NHSO₂CH₃ HCH₃ 170 NHCH₂CH═CHCO₂Et H CH₃ 171 NHCH₂CH═CHCO₂H H CH₃ 172 CONH₂ H CH₃173 CH₂CONH₂ H CH₃ 174 OCH₂CONH₂ H CH₃ 175 CN₄H H CH₃ 176 H CO₂Et CH₃177 H CO₂H CH₃ 178 H CH₂CO₂Et CH₃ 179 H CH₂CO₂H CH₃ 180 H OCH₂CO₂Et CH₃181 H OCH₂CO₂H CH₃ 182 H OCH₂CH₂CH₂PO(OEt)₂ CH₃ 183 H OCH₂CH₂CH₂PO(OH)₂CH₃ 184 H OCH₂C₆H₄CO₂Et CH₃ 185 H OCH₂C₆H₄CO₂H CH₃ 186 H NHCH₂CO₂Et CH₃187 H NHCH₂CO₂H CH₃ 188 H NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 189 HNHCH₂CH₂CH₂PO(OH)₂ CH₃ 190 H NHCH₂C₆H₄CO₂Et CH₃ 191 H NHCH₂C₆H₄CO₂H CH₃192 H NHCOCH₂CH₂CO₂Et CH₃ 193 H NHCOCH₂CH₂CO₂H CH₃ 194 H NHSO₂CH₃ CH₃195 H NHCH₂CH═CHCO₂Et CH₃ 196 H NHCH₂CH═CHCO₂H CH₃ 197 H CONH₂ CH₃ 198 HCH₂CONH₂ CH₃ 199 H OCH₂CONH₂ CH₃ 200 H CN₄H CH₃ 201 CO₂Et Cl H 202 CO₂HCl H 203 CH₂CO₂Et Cl H 204 CH₂CO₂H Cl H 205 OCH₂CO₂Et Cl H 206 OCH₂CO₂HCl H 207 OCH₂CH₂CH₂PO(OEt)₂ Cl H 208 OCH₂CH₂CH₂PO(OH)₂ Cl H 209OCH₂C₆H₄CO₂Et Cl H 210 OCH₂C₆H₄CO₂H Cl H 211 NHCH₂CO₂Et Cl H 212NHCH₂CO₂H Cl H 213 NHCH₂CH₂CH₂PO(OEt)₂ Cl H 214 NHCH₂CH₂CH₂PO(OH)₂ Cl H215 NHCH₂C₆H₄CO₂Et Cl H 216 NHCH₂C₆H₄CO₂H Cl H 217 NHCOCH₂CH₂CO₂Et Cl H218 NHCOCH₂CH₂CO₂H Cl H 219 NHSO₂CH₃ Cl H 220 NHCH₂CH═CHCO₂Et Cl H 221NHCH₂CH═CHCO₂H Cl H 222 CONH₂ Cl H 223 CH₂CONH₂ Cl H 224 OCH₂CONH₂ Cl H225 CN₄H Cl H 226 Cl CO₂Et H 227 Cl CO₂H H 228 Cl CH₂CO₂Et H 229 ClCH₂CO₂H H 230 Cl OCH₂CO₂Et H 231 Cl OCH₂CO₂H H 232 Cl OCH₂CH₂CH₂PO(OEt)₂H 233 Cl OCH₂CH₂CH₂PO(OH)₂ H 234 Cl OCH₂C₆H₄CO₂Et H 235 Cl OCH₂C₆H₄CO₂HH 236 Cl NHCH₂CO₂Et H 237 Cl NHCH₂CO₂H H 238 Cl NHCH₂CH₂CH₂PO(OEt)₂ H239 Cl NHCH₂CH₂CH₂PO(OH)₂ H 240 Cl NHCH₂C₆H₄CO₂Et H 241 Cl NHCH₂C₆H₄CO₂HH 242 Cl NHCOCH₂CH₂CO₂Et H 243 Cl NHCOCH₂CH₂CO₂H H 244 Cl NHSO₂CH₃ H 245Cl NHCH₂CH═CHCO₂Et H 246 Cl NHCH₂CH═CHCO₂H H 247 Cl CONH₂ H 248 ClCH₂CONH₂ H 249 Cl OCH₂CONH₂ H 250 Cl CN₄H H 251 CO₂Et Cl Cl 252 CO₂H ClCl 253 CH₂CO₂Et Cl Cl 254 CH₂CO₂H Cl Cl 255 OCH₂OC₂Et Cl Cl 256 OCH₂CO₂HCl Cl 257 OCH₂CH₂CH₂PO(OEt)₂ Cl Cl 258 OCH₂CH₂CH₂PO(OH)₂ Cl Cl 259OCH₂C₆H₄CO₂Et Cl Cl 260 OCH₂C₆H₄CO₂H Cl Cl 261 NHCH₂CO₂Et Cl Cl 262NHCH₂CO₂H Cl Cl 263 NHCH₂CH₂CH₂PO(OEt)₂ Cl Cl 264 NHCH₂CH₂CH₂PO(OH)₂ ClCl 265 NHCH₂C₆H₄CO₂Et Cl Cl 266 NHCH₂C₆H₄CO₂H Cl Cl 267 NHCOCH₂CH₂CO₂EtCl Cl 268 NHCOCH₂CH₂CO₂H Cl Cl 269 NHSO₂CH₃ Cl Cl 270 NHCH₂CH═CHCO₂Et ClCl 271 NHCH₂CH═CHCO₂H Cl Cl 272 CONH₂ Cl Cl 273 CH₂CONH₂ Cl Cl 274OCH₂CONH₂ Cl Cl 275 CN₄H Cl Cl 276 Cl CO₂Et Cl 277 Cl CO₂H Cl 278 ClCH₂CO₂Et Cl 279 Cl CH₂CO₂H Cl 280 Cl OCH₂CO₂Et Cl 281 Cl OCH₂CO₂H Cl 282Cl OCH₂CH₂CH₂PO(OEt)₂ Cl 283 Cl OCH₂CH₂CH₂PO(OH)₂ Cl 284 ClOCH₂C₆H₄CO₂Et Cl 285 Cl OCH₂C₆H₄CO₂H Cl 286 Cl NHCH₂CO₂Et Cl 287 ClNHCH₂CO₂H Cl 288 Cl NHCH₂CH₂CH₂PO(OEt)₂ Cl 289 Cl NHCH₂CH₂CH₂PO(OH)₂ Cl290 Cl NHCH₂C₆H₄CO₂Et Cl 291 Cl NHCH₂C₆H₄CO₂H Cl 292 Cl NHCOCH₂CH₂CO₂EtCl 293 Cl NHCOCH₂CH₂CO₂H Cl 294 Cl NHSO₂CH₃ Cl 295 Cl NHCH₂CH═CHCO₂Et Cl296 Cl NHCH₂CH═CHCO₂H Cl 297 Cl CONH₂ Cl 298 Cl CH₂CONH₂ Cl 299 ClOCH₂CONH₂ Cl 300 Cl CN₄H Cl 301 CO₂Et Cl OCH₃ 302 CO₂H Cl OCH₃ 303CH₂CO₂Et Cl OCH₃ 304 CH₂CO₂H Cl OCH₃ 305 OCH₂CO₂Et Cl OCH₃ 306 OCH₂CO₂HCl OCH₃ 307 OCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 308 OCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 309OCH₂C₆H₄CO₂Et Cl OCH₃ 310 OCH₂C₆H₄CO₂H Cl OCH₃ 311 NHCH₂CO₂Et Cl OCH₃312 NHCH₂CO₂H Cl OCH₃ 313 NHCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 314NHCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 315 NHCH₂C₆H₄CO₂Et Cl OCH₃ 316 NHCH₂C₆H₄CO₂HCl OCH₃ 317 NHCOCH₂CH₂CO₂Et Cl OCH₃ 318 NHCOCH₂CH₂CO₂H Cl OCH₃ 319NHSO₂CH₃ Cl OCH₃ 320 NHCH₂CH═CHCO₂Et Cl OCH₃ 321 NHCH₂CH═CHCO₂H Cl OCH₃322 CONH₂ Cl OCH₃ 323 CH₂CONH₂ Cl OCH₃ 324 OCH₂CONH₂ Cl OCH₃ 325 CN₄H ClOCH₃ 326 Cl CO₂Et OCH₃ 327 Cl CO₂H OCH₃ 328 Cl CH₂CO₂Et OCH₃ 329 ClCH₂CO₂H OCH₃ 330 Cl OCH₂CO₂Et OCH₃ 331 Cl OCH₂CO₂H OCH₃ 332 ClOCH₂CH₂CH₂PO(OEt)₂ OCH₃ 333 Cl OCH₂CH₂CH₂PO(OH)₂ OCH₃ 334 ClOCH₂C₆H₄CO₂Et OCH₃ 335 Cl OCH₂C₆H₄CO₂H OCH₃ 336 Cl NHCH₂CO₂Et OCH₃ 337Cl NHCH₂CO₂H OCH₃ 338 Cl NHCH₂CH₂CH₂PO(OEt)₂ OCH₃ 339 ClNHCH₂CH₂CH₂PO(OH)₂ OCH₃ 340 Cl NHCH₂C₆H₄CO₂Et OCH₃ 341 Cl NHCH₂C₆H₄CO₂HOCH₃ 342 Cl NHCOCH₂CH₂CO₂Et OCH₃ 343 Cl NHCOCH₂CH₂CO₂H OCH₃ 344 ClNHSO₂CH₃ OCH₃ 345 Cl NHCH₂CH═CHCO₂Et OCH₃ 346 Cl NHCH₂CH═CHCO₂H OCH₃ 347Cl CONH₂ OCH₃ 348 Cl CH₂CONH₂ OCH₃ 349 Cl OCH₂CONH₂ OCH₃ 350 Cl CN₄HOCH₃ 351 CO₂Et Cl CH₃ 352 CO₂H Cl CH₃ 353 CH₂CO₂Et Cl CH₃ 354 CH₂CO₂H ClCH₃ 355 OCH₂CO₂Et Cl CH₃ 356 OCH₂CO₂H Cl CH₃ 357 OCH₂CH₂CH₂PO(OEt)₂ ClCH₃ 358 OCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 359 OCH₂C₆H₄CO₂Et Cl CH₃ 360OCH₂C₆H₄CO₂H Cl CH₃ 361 NHCH₂CO₂Et Cl CH₃ 362 NHCH₂CO₂H Cl CH₃ 363NHCH₂CH₂CH₂PO(OEt)₂ Cl CH₃ 364 NHCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 365NHCH₂C₆H₄CO₂Et Cl CH₃ 366 NHCH₂C₆H₄CO₂H Cl CH₃ 367 NHCOCH₂CH₂CO₂Et ClCH₃ 368 NHCOCH₂CH₂CO₂H Cl CH₃ 369 NHSO₂CH₃ Cl CH₃ 370 NHCH₂CH═CHCO₂Et ClCH₃ 371 NHCH₂CH═CHCO₂H Cl CH₃ 372 CONH₂ Cl CH₃ 373 CH₂CONH₂ Cl CH₃ 374OCH₂CONH₂ Cl CH₃ 375 CN₄H Cl CH₃ 376 Cl CO₂Et CH₃ 377 Cl CO₂H CH₃ 378 ClCH₂CO₂Et CH₃ 379 Cl CH₂CO₂H CH₃ 380 Cl OCH₂CO₂Et CH₃ 381 Cl OCH₂CO₂H CH₃382 Cl OCH₂CH₂CH₂PO(OEt)₂ CH₃ 383 Cl OCH₂CH₂CH₂PO(OH)₂ CH₃ 384 ClOCH₂C₆H₄CO₂Et CH₃ 385 Cl OCH₂C₆H₄CO₂H CH₃ 386 Cl NHCH₂CO₂Et CH₃ 387 ClNHCH₂CO₂H CH₃ 388 Cl NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 389 Cl NHCH₂CH₂CH₂PO(OH)₂CH₃ 390 Cl NHCH₂C₆H₄CO₂Et CH₃ 391 Cl NHCH₂C₆H₄CO₂H CH₃ 392 ClNHCOCH₂CH₂CO₂Et CH₃ 393 Cl NHCOCH₂CH₂CO₂H CH₃ 394 Cl NHSO₂CH₃ CH₃ 395 ClNHCH₂CH═CHCO₂Et CH₃ 396 Cl NHCH₂CH═CHCO₂H CH₃ 397 Cl CONH₂ CH₃ 398 ClCH₂CONH₂ CH₃ 399 Cl OCH₂CONH₂ CH₃ 400 Cl CN₄H CH₃

TABLE 4

Ex. # Y V Q n 1 Cl CO₂Et N 1 2 Cl CO₂H N 1 3 Cl CONH₂ N 1 4 Cl CN₄H N 15 CH₃ CO₂Et N 1 6 CH₃ CO₂H N 1 7 CH₃ CONH₂ N 1 8 CH₃ CN₄H N 1 9 OCH₃CO₂Et N 1 10 OCH₃ CO₂H N 1 11 OCH₃ CONH₂ N 1 12 OCH₃ CN₄H N 1 13CH(CH₃)₂ CO₂Et N 1 14 CH(CH₃)₂ CO₂H N 1 15 CH(CH₃)₂ CONH₂ N 1 16CH(CH₃)₂ CN₄H N 1 17 Cl CO₂Et N 2 18 Cl CO₂H N 2 19 Cl CONH₂ N 2 20 ClCN₄H N 2 21 CH₃ CO₂Et N 2 22 CH₃ CO₂H N 2 23 CH₃ CONH₂ N 2 24 CH₃ CN₄H N2 25 OCH₃ CO₂Et N 2 26 OCH₃ CO₂H N 2 27 OCH₃ CONH₂ N 2 28 OCH₃ CN₄H N 229 CH(CH₃)₂ CO₂Et N 2 30 CH(CH₃)₂ CO₂H N 2 31 CH(CH₃)₂ CONH₂ N 2 32CH(CH₃)₂ CN₄H N 2 33 Cl CO₂Et CH 1 34 Cl CO₂H CH 1 35 Cl CONH₂ CH 1 36Cl CN₄H CH 1 37 CH₃ CO₂Et CH 1 38 CH₃ CO₂H CH 1 39 CH₃ CONH₂ CH 1 40 CH₃CN₄H CH 1 41 OCH₃ CO₂Et CH 1 42 OCH₃ CO₂H CH 1 43 OCH₃ CONH₂ CH 1 44OCH₃ CN₄H CH 1 45 CH(CH₃)₂ CO₂Et CH 1 46 CH(CH₃)₂ CO₂H CH 1 47 CH(CH₃)₂CONH₂ CH 1 48 CH(CH₃)₂ CN₄H CH 1 49 Cl CO₂Et CH 2 50 Cl CO₂H CH 2 51 ClCONH₂ CH 2 52 Cl CN₄H CH 2 53 CH₃ CO₂Et CH 2 54 CH₃ CO₂H CH 2 55 CH₃CONH₂ CH 2 56 CH₃ CN₄H CH 2 57 OCH₃ CO₂Et CH 2 58 OCH₃ CO₂H CH 2 59 OCH₃CONH₂ CH 2 60 OCH₃ CN₄H CH 2 61 CH(CH₃)₂ CO₂Et CH 2 62 CH(CH₃)₂ CO₂H CH2 63 CH(CH₃)₂ CONH₂ CH 2 64 CH(CH₃)₂ CN₄H CH 2

TABLE 5a

Ex. # Y R A m 1 Cl Et H 0 2 Cl H H 0 3 Cl Et H 1 4 Cl H H 1 5 Cl Et H 36 Cl H H 3 7 Cl Et CH₃ 0 8 Cl H CH₃ 0 9 Cl Et CH₃ 2 10 Cl H CH₃ 2 11 ClEt C₆H₅ 0 12 Cl H C₆H₅ 0 13 Cl Et CH₂C₆H₅ 0 14 Cl H CH₂C₆H₅ 0 15 CH₃ EtH 0 16 CH₃ H H 0 17 CH₃ Et H 1 18 CH₃ H H 1 19 CH₃ Et H 3 20 CH₃ H H 321 CH₃ Et CH₃ 0 22 CH₃ H CH₃ 0 23 CH₃ Et CH₃ 2 24 CH₃ H CH₃ 2 25 CH₃ EtC₆H₅ 0 26 CH₃ H C₆H₅ 0 27 CH₃ Et CH₂C₆H₅ 0 28 CH₃ H CH₂C₆H₅ 0 29 OCH₃ EtH 0 30 OCH₃ H H 0 31 OCH₃ Et H 1 32 OCH₃ H H 1 33 OCH₃ Et H 3 34 OCH₃ HH 3 35 OCH₃ Et CH₃ 0 36 OCH₃ H CH₃ 0 37 OCH₃ Et CH₃ 2 38 OCH₃ H CH₃ 2 39OCH₃ Et C₆H₅ 0 40 OCH₃ H C₆H₅ 0 41 OCH₃ Et CH₂C₆H₅ 0 42 OCH₃ H CH₂C₆H₅ 043 CH(CH₃)₂ Et H 0 44 CH(CH₃)₂ H H 0 45 CH(CH₃)₂ Et H 1 46 CH(CH₃)₂ H H1 47 CH(CH₃)₂ Et H 3 48 CH(CH₃)₂ H H 3 49 CH(CH₃)₂ Et CH₃ 0 50 CH(CH₃)₂H CH₃ 0 51 CH(CH₃)₂ Et CH₃ 2 52 CH(CH₃)₂ H CH₃ 2 53 CH(CH₃)₂ Et C₆H₅ 054 CH(CH₃)₂ H C₆H₅ 0 55 CH(CH₃)₂ Et CH₂C₆H₅ 0 56 CH(CH₃)₂ H CH₂C₆H₅ 0 57Cl Et C(CH₃)₃ 0 58 Cl H C(CH₃)₃ 0 59 Cl Et C(CH₃)₃ 1 60 Cl H C(CH₃)₃ 161 Cl Et C(CH₃)₃ 2 62 Cl H C(CH₃)₃ 2

TABLE 5b

Ex. # Y R A m 1 Cl Et H 0 2 Cl H H 0 3 Cl Et H 1 4 Cl H H 1 5 Cl Et H 36 Cl H H 3 7 Cl Et C(CH₃)₃ 0 8 Cl H C(CH₃)₃ 0 9 Cl Et C(CH₃)₃ 2 10 Cl HC(CH₃)₃ 2 11 Cl Et C₆H₅ 0 12 Cl H C₆H₅ 0 13 Cl Et CH₂C₆H₅ 0 14 Cl HCH₂C₆H₅ 0 15 CH₃ Et H 0 16 CH₃ H H 0 17 CH₃ Et H 1 18 CH₃ H H 1 19 CH₃Et H 3 20 CH₃ H H 3 21 CH₃ Et C(CH₃)₃ 0 22 CH₃ H C(CH₃)₃ 0 23 CH₃ EtC(CH₃)₃ 2 24 CH₃ H C(CH₃)₃ 2 25 CH₃ Et C₆H₅ 0 26 CH₃ H C₆H₅ 0 27 CH₃ EtCH₂C₆H₅ 0 28 CH₃ H CH₂C₆H₅ 0 29 OCH₃ Et H 0 30 OCH₃ H H 0 31 OCH₃ Et H 132 OCH₃ H H 1 33 OCH₃ Et H 3 34 OCH₃ H H 3 35 OCH₃ Et C(CH₃)₃ 0 36 OCH₃H C(CH₃)₃ 0 37 OCH₃ Et C(CH₃)₃ 2 38 OCH₃ H C(CH₃)₃ 2 39 OCH₃ Et C₆H₅ 040 OCH₃ H C₆H₅ 0 41 OCH₃ Et CH₂C₆H₅ 0 42 OCH₃ H CH₂C₆H₅ 0 43 CH(CH₃)₂ EtH 0 44 CH(CH₃)₂ H H 0 45 CH(CH₃)₂ Et H 1 46 CH(CH₃)₂ H H 1 47 CH(CH₃)₂Et H 3 48 CH(CH₃)₂ H H 3 49 CH(CH₃)₂ Et C(CH₃)₃ 0 50 CH(CH₃)₂ H C(CH₃)₃0 51 CH(CH₃)₂ Et C(CH₃)₃ 2 52 CH(CH₃)₂ H C(CH₃)₃ 2 53 CH(CH₃)₂ Et C₆H₅ 054 CH(CH₃)₂ H C₆H₅ 0 55 CH(CH₃)₂ Et CH₂C₆H₅ 0 56 CH(CH₃)₂ H CH₂C₆H₅ 0

TABLE 5c

Ex. # Y R A m 1 Cl Et H 0 2 Cl H H 0 3 Cl Et H 1 4 Cl H H 1 5 Cl Et H 36 Cl H H 3 7 Cl Et C(CH₃)₃ 0 8 Cl H C(CH₃)₃ 0 9 Cl Et C(CH₃)₃ 2 10 Cl HC(CH₃)₃ 2 11 Cl Et C₆H₅ 0 12 Cl H C₆H₅ 0 13 Cl Et CH₂C₆H₅ 0 14 Cl HCH₂C₆H₅ 0 15 CH₃ Et H 0 16 CH₃ H H 0 17 CH₃ Et H 1 18 CH₃ H H 1 19 CH₃Et H 3 20 CH₃ H H 3 21 CH₃ Et C(CH₃)₃ 0 22 CH₃ H C(CH₃)₃ 0 23 CH₃ EtC(CH₃)₃ 2 24 CH₃ H C(CH₃)₃ 2 25 CH₃ Et C₆H₅ 0 26 CH₃ H C₆H₅ 0 27 CH₃ EtCH₂C₆H₅ 0 28 CH₃ H CH₂C₆H₅ 0 29 OCH₃ Et H 0 30 OCH₃ H H 0 31 OCH₃ Et H 132 OCH₃ H H 1 33 OCH₃ Et H 3 34 OCH₃ H H 3 35 OCH₃ Et C(CH₃)₃ 0 36 OCH₃H C(CH₃)₃ 0 37 OCH₃ Et C(CH₃)₃ 2 38 OCH₃ H C(CH₃)₃ 2 39 OCH₃ Et C₆H₅ 040 OCH₃ H C₆H₅ 0 41 OCH₃ Et CH₂C₆H₅ 0 42 OCH₃ H CH₂C₆H₅ 0 43 CH(CH₃)₂ EtH 0 44 CH(CH₃)₂ H H 0 45 CH(CH₃)₂ Et H 1 46 CH(CH₃)₂ H H 1 47 CH(CH₃)₂Et H 3 48 CH(CH₃)₂ H H 3 49 CH(CH₃)₂ Et C(CH₃)₃ 0 50 CH(CH₃)₂ H C(CH₃)₃0 51 CH(CH₃)₂ Et C(CH₃)₃ 2 52 CH(CH₃)₂ H C(CH₃)₃ 2 53 CH(CH₃)₂ Et C₆H₅ 054 CH(CH₃)₂ H C₆H₅ 0 55 CH(CH₃)₂ Et CH₂C₆H₅ 0 56 CH(CH₃)₂ H CH₂C₆H₅ 0

TABLE 5d

Ex. # Y R A m 1 Cl Et H 0 2 Cl H H 0 3 Cl Et H 1 4 Cl H H 1 5 Cl Et H 36 Cl H H 3 7 Cl Et CH₃ 0 8 Cl H CH₃ 0 9 Cl Et CH₃ 2 10 Cl H CH₃ 2 11 ClEt C₆H₅ 0 12 Cl H C₆H₅ 0 13 Cl Et CH₂C₆H₅ 0 14 Cl H CH₂C₆H₅ 0 15 CH₃ EtH 0 16 CH₃ H H 0 17 CH₃ Et H 1 18 CH₃ H H 1 19 CH₃ Et H 3 20 CH₃ H H 321 CH₃ Et C(CH₃)₃ 0 22 CH₃ H C(CH₃)₃ 0 23 CH₃ Et C(CH₃)₃ 2 24 CH₃ HC(CH₃)₃ 2 25 CH₃ Et C₆H₅ 0 26 CH₃ H C₆H₅ 0 27 CH₃ Et CH₂C₆H₅ 0 28 CH₃ HCH₂C₆H₅ 0 29 OCH₃ Et H 0 30 OCH₃ H H 0 31 OCH₃ Et H 1 32 OCH₃ H H 1 33OCH₃ Et H 3 34 OCH₃ H H 3 35 OCH₃ Et C(CH₃)₃ 0 36 OCH₃ H C(CH₃)₃ 0 37OCH₃ Et C(CH₃)₃ 2 38 OCH₃ H C(CH₃)₃ 2 39 OCH₃ Et C₆H₅ 0 40 OCH₃ H C₆H₅ 041 OCH₃ Et CH₂C₆H₅ 0 42 OCH₃ H CH₂C₆H₅ 0 43 CH(CH₃)₂ Et H 0 44 CH(CH₃)₂H H 0 45 CH(CH₃)₂ Et H 1 46 CH(CH₃)₂ H H 1 47 CH(CH₃)₂ Et H 3 48CH(CH₃)₂ H H 3 49 CH(CH₃)₂ Et C(CH₃)₃ 0 50 CH(CH₃)₂ H C(CH₃)₃ 0 51CH(CH₃)₂ Et C(CH₃)₃ 2 52 CH(CH₃)₂ H C(CH₃)₃ 2 53 CH(CH₃)₂ Et C₆H₅ 0 54CH(CH₃)₂ H C₆H₅ 0 55 CH(CH₃)₂ Et CH₂C₆H₅ 0 56 CH(CH₃)₂ H CH₂C₆H₅ 0

TABLE 5e

Ex. # Y R A m 1 Cl Et H 0 2 Cl H H 0 3 Cl Et H 1 4 Cl H H 1 5 Cl Et H 36 Cl H H 3 7 Cl Et CH₃ 0 8 Cl H CH₃ 0 9 Cl Et CH₃ 2 10 Cl H CH₃ 2 11 ClEt C₆H₅ 0 12 Cl H C₆H₅ 0 13 Cl Et CH₂C₆H₅ 0 14 Cl H CH₂C₆H₅ 0 15 CH₃ EtH 0 16 CH₃ H H 0 17 CH₃ Et H 1 18 CH₃ H H 1 19 CH₃ Et H 3 20 CH₃ H H 321 CH₃ Et CH₃ 0 22 CH₃ H CH₃ 0 23 CH₃ Et CH₃ 2 24 CH₃ H CH₃ 2 25 CH₃ EtC₆H₅ 0 26 CH₃ H C₆H₅ 0 27 CH₃ Et CH₂C₆H₅ 0 28 CH₃ H CH₂C₆H₅ 0 29 OCH₃ EtH 0 30 OCH₃ H H 0 31 OCH₃ Et H 1 32 OCH₃ H H 1 33 OCH₃ Et H 3 34 OCH₃ HH 3 35 OCH₃ Et CH₃ 0 36 OCH₃ H CH₃ 0 37 OCH₃ Et CH₃ 2 38 OCH₃ H CH₃ 2 39OCH₃ Et C₆H₅ 0 40 OCH₃ H C₆H₅ 0 41 OCH₃ Et CH₂C₆H₅ 0 42 OCH₃ H CH₂C₆H₅ 043 CH(CH₃)₂ Et H 0 44 CH(CH₃)₂ H H 0 45 CH(CH₃)₂ Et H 1 46 CH(CH₃)₂ H H1 47 CH(CH₃)₂ Et H 3 48 CH(CH₃)₂ H H 3 49 CH(CH₃)₂ Et CH₃ 0 50 CH(CH₃)₂H CH₃ 0 51 CH(CH₃)₂ Et CH₃ 2 52 CH(CH₃)₂ H CH₃ 2 53 CH(CH₃)₂ Et C₆H₅ 054 CH(CH₃)₂ H C₆H₅ 0 55 CH(CH₃)₂ Et CH₂C₆H₅ 0 56 CH(CH₃)₂ H CH₂C₆H₅ 0

TABLE 5f

Ex. # Y R Substituent position m 1 Cl Et 2 0 2 Cl H 2 0 3 Cl Et 2 0 4 ClH 2 0 5 Cl Et 2 1 6 Cl H 2 1 7 Cl Et 2 1 8 Cl H 2 1 9 CH₃ Et 2 0 10 CH₃H 2 0 11 CH₃ Et 2 0 12 CH₃ H 2 0 13 CH₃ Et 2 1 14 CH₃ H 2 1 15 CH₃ Et 21 16 CH₃ H 2 1 17 OCH₃ Et 2 0 18 OCH₃ H 2 0 19 OCH₃ Et 2 0 20 OCH₃ H 2 021 OCH₃ Et 2 1 22 OCH₃ H 2 1 23 OCH₃ Et 2 1 24 OCH₃ H 2 1 25 CH(CH₃)₂ Et2 0 26 CH(CH₃)₂ H 2 0 27 CH(CH₃)₂ Et 2 0 28 CH(CH₃)₂ H 2 0 29 CH(CH₃)₂Et 2 1 30 CH(CH₃)₂ H 2 1 31 CH(CH₃)₂ Et 2 1 32 CH(CH₃)₂ H 2 1 33 Cl Et 30 34 Cl H 3 0 35 Cl Et 3 0 36 Cl H 3 0 37 Cl Et 3 1 38 Cl H 3 1 39 Cl Et3 1 40 Cl H 3 1 41 CH₃ Et 3 0 42 CH₃ H 3 0 43 CH₃ Et 3 0 44 CH₃ H 3 0 45CH₃ Et 3 1 46 CH₃ H 3 1 47 CH₃ Et 3 1 48 CH₃ H 3 1 49 OCH₃ Et 3 0 50OCH₃ H 3 0 51 OCH₃ Et 3 0 52 OCH₃ H 3 0 53 OCH₃ Et 3 1 54 OCH₃ H 3 1 55OCH₃ Et 3 1 56 OCH₃ H 3 1 57 CH(CH₃)₂ Et 3 0 58 CH(CH₃)₂ H 3 0 59CH(CH₃)₂ Et 3 0 60 CH(CH₃)₂ H 3 0 61 CH(CH₃)₂ Et 3 1 62 CH(CH₃)₂ H 3 163 CH(CH₃)₂ Et 3 1 64 CH(CH₃)₂ H 3 1 65 Cl Et 4 0 66 Cl H 4 0 67 Cl Et 40 68 Cl H 4 0 69 Cl Et 4 1 70 Cl H 4 1 71 Cl Et 4 1 72 Cl H 4 1 73 CH₃Et 4 0 74 CH₃ H 4 0 75 CH₃ Et 4 0 76 CH₃ H 4 0 77 CH₃ Et 4 1 78 CH₃ H 41 79 CH₃ Et 4 1 80 CH₃ H 4 1 81 OCH₃ Et 4 0 82 OCH₃ H 4 0 83 OCH₃ Et 4 084 OCH₃ H 4 0 85 OCH₃ Et 4 1 86 OCH₃ H 4 1 87 OCH₃ Et 4 1 88 OCH₃ H 4 189 CH(CH₃)₂ Et 4 0 90 CH(CH₃)₂ H 4 0 91 CH(CH₃)₂ Et 4 0 92 CH(CH₃)₂ H 40 93 CH(CH₃)₂ Et 4 1 94 CH(CH₃)₂ H 4 1 95 CH(CH₃)₂ Et 4 1 96 CH(CH₃)₂ H4 1

TABLE 5g

Ex. # Y′ R Substituent position m 1 CH₃ Et 2 0 2 CH₃ H 2 0 3 CH₃ Et 2 04 CH₃ H 2 0 5 CH₃ Et 2 1 6 CH₃ H 2 1 7 CH₃ Et 2 1 8 CH₃ H 2 1 9 OCH₃ Et2 0 10 OCH₃ H 2 0 11 OCH₃ Et 2 0 12 OCH₃ H 2 0 13 OCH₃ Et 2 1 14 OCH₃ H2 1 15 OCH₃ Et 2 1 16 OCH₃ H 2 1 17 CH(CH₃)₂ Et 2 0 18 CH(CH₃)₂ H 2 0 19CH(CH₃)₂ Et 2 0 20 CH(CH₃)₂ H 2 0 21 CH(CH₃)₂ Et 2 1 22 CH(CH₃)₂ H 2 123 CH(CH₃)₂ Et 2 1 24 CH(CH₃)₂ H 2 1 25 CH₃ Et 3 0 26 CH₃ H 3 0 27 CH₃Et 3 0 28 CH₃ H 3 0 29 CH₃ Et 3 1 30 CH₃ H 3 1 31 CH₃ Et 3 1 32 CH₃ H 31 33 OCH₃ Et 3 0 34 OCH₃ H 3 0 35 OCH₃ Et 3 0 36 OCH₃ H 3 0 37 OCH₃ Et 31 38 OCH₃ H 3 1 39 OCH₃ Et 3 1 40 OCH₃ H 3 1 41 CH(CH₃)₂ Et 3 0 42CH(CH₃)₂ H 3 0 43 CH(CH₃)₂ Et 3 0 44 CH(CH₃)₂ H 3 0 45 CH(CH₃)₂ Et 3 146 CH(CH₃)₂ H 3 1 47 CH(CH₃)₂ Et 3 1 48 CH(CH₃)₂ H 3 1 49 CH₃ Et 4 0 50CH₃ H 4 0 51 CH₃ Et 4 0 52 CH₃ H 4 0 53 CH₃ Et 4 1 54 CH₃ H 4 1 55 CH₃Et 4 1 56 CH₃ H 4 1 57 OCH₃ Et 4 0 58 OCH₃ H 4 0 59 OCH₃ Et 4 0 60 OCH₃H 4 0 61 OCH₃ Et 4 1 62 OCH₃ H 4 1 63 OCH₃ Et 4 1 64 OCH₃ H 4 1 65CH(CH₃)₂ Et 4 0 66 CH(CH₃)₂ H 4 0 67 CH(CH₃)₂ Et 4 0 68 CH(CH₃)₂ H 4 069 CH(CH₃)₂ Et 4 1 70 CH(CH₃)₂ H 4 1 71 CH(CH₃)₂ Et 4 1 72 CH(CH₃)₂ H 41

TABLE 6a

Ex. # Y Q′ A m 1 Cl O H 0 2 Cl NH H 0 3 Cl O H 1 4 Cl NH H 1 5 Cl O H 36 Cl NH H 3 7 Cl O CH₃ 0 8 Cl NH CH₃ 0 9 Cl O CH₃ 2 10 Cl NH CH₃ 2 11 ClO C₆H₅ 0 12 Cl NH C₆H₅ 0 13 Cl O CH₂C₆H₅ 0 14 Cl NH CH₂C₆H₅ 0 15 CH₃ O H0 16 CH₃ NH H 0 17 CH₃ O H 1 18 CH₃ NH H 1 19 CH₃ O H 3 20 CH₃ NH H 3 21CH₃ O CH₃ 0 22 CH₃ NH CH₃ 0 23 CH₃ O CH₃ 2 24 CH₃ NH CH₃ 2 25 CH₃ O C₆H₅0 26 CH₃ NH C₆H₅ 0 27 CH₃ O CH₂C₆H₅ 0 28 CH₃ NH CH₂C₆H₅ 0 29 OCH₃ O H 030 OCH₃ NH H 0 31 OCH₃ O H 1 32 OCH₃ NH H 1 33 OCH₃ O H 3 34 OCH₃ NH H 335 OCH₃ O CH₃ 0 36 OCH₃ NH CH₃ 0 37 OCH₃ O CH₃ 2 38 OCH₃ NH CH₃ 2 39OCH₃ O C₆H₅ 0 40 OCH₃ NH C₆H₅ 0 41 OCH₃ O CH₂C₆H₅ 0 42 OCH₃ NH CH₂C₆H₅ 043 CH(CH₃)₂ O H 0 44 CH(CH₃)₂ NH H 0 45 CH(CH₃)₂ O H 1 46 CH(CH₃)₂ NH H1 47 CH(CH₃)₂ O H 3 48 CH(CH₃)₂ NH H 3 49 CH(CH₃)₂ O CH₃ 0 50 CH(CH₃)₂NH CH₃ 0 51 CH(CH₃)₂ O CH₃ 2 52 CH(CH₃)₂ NH CH₃ 2 53 CH(CH₃)₂ O C₆H₅ 054 CH(CH₃)₂ NH C₆H₅ 0 55 CH(CH₃)₂ O CH₂C₆H₅ 0 56 CH(CH₃)₂ NH CH₂C₆H₅ 057 Cl O C(CH₃)₃ 0 58 Cl NH C(CH₃)₃ 0 59 Cl O C(CH₃)₃ 1 60 Cl NH C(CH₃)₃1 61 Cl O C(CH₃)₃ 2 62 Cl NH C(CH₃)₃ 2

TABLE 6b

Ex. # Y Q′ A m 1 Cl O H 0 2 Cl NH H 0 3 Cl O H 1 4 Cl NH H 1 5 Cl O H 36 Cl NH H 3 7 Cl O C(CH₃)₃ 0 8 Cl NH C(CH₃)₃ 0 9 Cl O C(CH₃)₃ 2 10 Cl NHC(CH₃)₃ 2 11 Cl O C₆H₅ 0 12 Cl NH C₆H₅ 0 13 Cl O CH₂C₆H₅ 0 14 Cl NHCH₂C₆H₅ 0 15 CH₃ O H 0 16 CH₃ NH H 0 17 CH₃ O H 1 18 CH₃ NH H 1 19 CH₃ OH 3 20 CH₃ NH H 3 21 CH₃ O C(CH₃)₃ 0 22 CH₃ NH C(CH₃)₃ 0 23 CH₃ OC(CH₃)₃ 2 24 CH₃ NH C(CH₃)₃ 2 25 CH₃ O C₆H₅ 0 26 CH₃ NH C₆H₅ 0 27 CH₃ OCH₂C₆H₅ 0 28 CH₃ NH CH₂C₆H₅ 0 29 OCH₃ O H 0 30 OCH₃ NH H 0 31 OCH₃ O H 132 OCH₃ NH H 1 33 OCH₃ O H 3 34 OCH₃ NH H 3 35 OCH₃ O C(CH₃)₃ 0 36 OCH₃NH C(CH₃)₃ 0 37 OCH₃ O C(CH₃)₃ 2 38 OCH₃ NH C(CH₃)₃ 2 39 OCH₃ O C₆H₅ 040 OCH₃ NH C₆H₅ 0 41 OCH₃ O CH₂C₆H₅ 0 42 OCH₃ NH CH₂C₆H₅ 0 43 CH(CH₃)₂ OH 0 44 CH(CH₃)₂ NH H 0 45 CH(CH₃)₂ O H 1 46 CH(CH₃)₂ NH H 1 47 CH(CH₃)₂O H 3 48 CH(CH₃)₂ NH H 3 49 CH(CH₃)₂ O C(CH₃)₃ 0 50 CH(CH₃)₂ NH C(CH₃)₃0 51 CH(CH₃)₂ O C(CH₃)₃ 2 52 CH(CH₃)₂ NH C(CH₃)₃ 2 53 CH(CH₃)₂ O C₆H₅ 054 CH(CH₃)₂ NH C₆H₅ 0 55 CH(CH₃)₂ O CH₂C₆H₅ 0 56 CH(CH₃)₂ NH CH₂C₆H₅ 0

Numerous modifications and variations of the present invention arepossible in light of the above teachings. It is therefore to beunderstood that within the scope of the appended claims, the inventionmay be practiced otherwise that as specifically described herein.

1. A compound of formula I or a stereoisomer or pharmaceuticallyacceptable salt thereof:

wherein: X and Y are independently selected from H, halogen, C₁₋₆ alkyl,NO₂, CF₃, NR₂, OR, CO₂R, (CH₂)_(n)CO₂R, O(CH₂)_(n)CO₂R, OCH₂CH═CHCO₂R,CH₂O(CH₂)_(n)CO₂R, CH₂OCH₂CH═CHCO₂R, O(CH₂)_(n)PO(OR)₂,CH₂O(CH₂)_(n)PO(OR)₂, NR^(a)(CH₂)_(n)CO₂R, NR^(a)(CH₂)_(n)PO(OR)₂,NR^(a)CH₂CH═CHCO₂R, NR^(a)SO₂CH₃, NR^(a)CO(CH₂)_(n)CO₂R,O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)C₆H₄CO₂R,O(CH₂)_(n)C₆H₄CONH₂, O(CH₂)_(n)C₆H₄(CH₂)_(n)CONH₂,CH₂O(CH₂)_(n)C₆H₄CONH₂, O(CH₂)_(n)C₆H₄-tetrazole,CH₂O(CH₂)_(n)C₆H₄-tetrazole, O(CH₂)_(n)C₆H₄(CH₂)_(n)-tetrazole,NR^(a)(CH₂)_(n)C₆H₄CO₂R, CH₂NR^(a)(CH₂)_(n)C₆H₄CO₂R,NR^(a)(CH₂)_(n)C₆H₄CONH₂, CH₂NR^(a)(CH₂)_(n)C₆H₄CONH₂,NR^(a)(CH₂)_(n)C₆H₄-tetrazole, CH₂NR^(a)(CH₂)_(n)C₆H₄-tetrazole, —CN,(CH₂)_(m)C(NH)NH₂, CONR₂, (CH₂)_(n)CONR₂, O(CH₂)_(n)CONR₂,CH₂O(CH₂)_(n)CONH₂, NR^(a)(CH₂)_(n)CONR₂, OCH₂CH═CHCONR₂,CH₂OCH₂CH═CHCONR₂, NR^(a)CH₂CH═CHCONR₂, -tetrazole, O(CH₂CH₂O)_(p)R,NR^(a)(CH₂CH₂O)_(p)R, and SO₂NR^(a)CH₃; X′ and Y′ are independentlyselected from H, halogen, C₁₋₆alkyl, NO₂, CF₃, NR₂, OR, CO₂R,(CH₂)_(n)CO₂R, O(CH₂)_(n)CO₂R, OCH₂CH═CHCO₂R, CH₂O(CH₂)_(n)CO₂R,CH₂OCH₂CH═CHCO₂R, O(CH₂)PO(OR)₂, CH₂O(CH₂)_(n)PO(OR)₂,NR^(a)(CH₂)_(n)CO₂R, NR^(a)(CH₂)PO(OR)₂, NR^(a)CH₂CH═CHCO₂R,NR^(a)SO₂CH₃, NR^(a)CO(CH₂)_(n)CO₂R, O(CH₂)_(n)C₆H₄CO₂R,O(CH₂)_(n)C₆H₄(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄(CH₂)_(n)CONH₂, CH₂O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄-tetrazole, CH₂O(CH₂)_(n)C₆H₄-tetrazole,O(CH₂)_(n)C₆H₄(CH₂)_(n)-tetrazole, NR^(a)(CH₂)_(n)C₆H₄CO₂R,CH₂NR^(a)(CH₂)_(n)C₆H₄CO₂R, NR^(a)(CH₂)_(n)C₆H₄CONH₂,CH₂NR^(a)(CH₂)_(n)C₆H₄CONH₂, NR^(a)(CH₂)_(n)C₆H₄-tetrazole,CH₂NR^(a)(CH₂)_(n)C₆H₄tetrazole, —CN, (CH₂)_(m)C(NH)NH₂, CONR₂,(CH₂)_(n)CONR₂, O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONH₂,NR^(a)(CH₂)_(n)CONR₂, OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂,NR^(a)CH₂CH═CHCONR₂, -tetrazole, O(CH₂CH₂O)_(p)R, NR^(a)(CH₂CH₂O)_(p)R,and SO₂NR^(a)CH₃; A is selected from H, C₁₋₆ alkyl,(CH₂)_(m)-C₃₋₆-cycloalkyl, (CH₂)_(m)-heteroaryl, and (CH₂)_(m)-aryl,wherein each aryl and heteroaryl is substituted with 0-1 groups selectedfrom CF₃, halogen, C₁₋₄ alkyl, -CN, CONR₂, NO₂, NR₂, and OR; R′ is

R″ is selected from H, C₁₋₆ alkyl and (CH₂)₀₋₆ aryl; Z is selected fromH, C₁₋₆ alkyl, aryl, NR₂, OR, —CN, (CH₂)_(m)C(NH)NH₂, CO₂R,(CH₂)_(n)CO₂R, O(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CO₂R, NR^(a)CH(A)CO₂R,CH₂NR^(a)CH(A)CO₂R, NR^(a)(CH₂)_(n)CO₂R CH₂NR^(a)(CH₂)_(n)CO₂ROCH₂CH═CHCO₂R, CH₂OCH₂CH═CHCO₂R, O(CH₂)PO(OR)₂, CH₂O(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)C₆H₄CO₂R, CH₂O(CH₂)_(n)C₆H₄CO₂R, CONR₂, (CH₂)_(n)CONR₂,O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONR₂, OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂,CH₂NR^(a)(CH₂)_(n)tetrazole, CH₂O(CH₂)_(n)tetrazole, and(CH₂)_(m)tetrazole; Q is selected from N, CH, and CQ′; Q′ is selectedfrom H, CO₂R, (CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CO₂R, CH₂OCH₂CH═CHCO₂R,CH₂O(CH₂)_(n)PO(OR)₂, CONR₂, (CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONR₂,CH₂OCH₂CH═CHCONR₂, and (CH₂)_(m)tetrazole; V is selected from H, C₁₋₆alkyl, C₂₋₆ alkenyl, CF₃, aryl, —CN, (CH₂)_(m)C(NH)NH₂, (CH₂)_(m)CO₂R,(CH₂)_(m)CONR₂, (CH₂)_(m)-tetrazole,(CH₂)_(m)CONR^(a)CH(A)-(CH₂)_(m)CO₂R,(CH₂)_(m)CONR^(a)(CH₂)_(m)-phenyl-(CH₂)_(m)CO₂R,(CH₂)_(m)CONR^(a)(CH₂)_(m)-phenyl-(CH₂)_(m)-tetrazole,CH₂O(CH₂)_(n)CO₂R, CH₂NR^(a)(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CONH₂,CH₂NR^(a)(CH₂)_(n)CONH₂, and CH₂O(CH₂)_(n)tetrazole; R is independentlyselected from H, C₁₋₆ alkyl; R^(a) is independently selected from H,C₁₋₆ alkyl, C₂₋₆ alkenyl, and C₂₋₆ alkynyl; m is selected from 0,1,2,3,and 4; n is selected from 1,2,3, and 4; and, p is selected from1,2,3,4,5,6,7,8,9,10,11, and 12; provided that at least one of thefollowing is satisfied: (a) at least one of X, Y, X′, and Y′ is otherthan H, halogen, C₁₋₆ alkyl, NO₂, —CN, CF₃, OR, and phenyl; (c) Z ispresent and is other than H, -C₁₋₆ alkyl, aryl, NR₂, and OR; (d) Q ispresent and is CQ′ where Q′ is other than H; and/or (e) V is other thanH, —CN, CF₃, C₂₋₆ alkenyl, aryl, and C₁₋₆ alkyl.
 2. A compound of claim1, wherein the compound is of formula II or a stereoisomer orpharmaceutically acceptable salt thereof:


3. A compound of claim 1, wherein the compound is of formula IIa or astereoisomer or pharmaceutically acceptable salt thereof:


4. A compound of claim 2, wherein: X and Y are independently selectedfrom H, halogen, C₁₋₄ alkyl, CF₃, —CN, NO₂, NR₂, and OR; X′ and Y′ areindependently selected from H, halogen, C₁₋₄ alkyl, CF₃, —CN, NO₂, NR₂,and OR; Z is selected from (CH₂)_(m)C(NH)NH₂, (CH₂)_(m)CO₂R,O(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CO₂R, NR^(a)CH(A)CO₂R, CH₂NR^(a)CH(A)CO₂R,NR^(a)(CH₂)_(n)CO₂R CH₂NR^(a)(CH₂)_(n)CO₂R OCH₂CH═CHCO₂R,CH₂OCH₂CH═CHCO₂R, O(CH₂)_(n)PO (OR)₂, CH₂O(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)C₆H₄CO₂R, CH₂O(CH₂)_(n)C₆H₄CO₂R, (CH₂)_(m)CONR₂,O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONR₂, OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂,CH₂NR^(a)(CH₂)_(n)tetrazole, CH₂O(CH₂)_(n)tetrazole, and(CH₂)_(m)tetrazole; Q is selected from N and CH; V is selected from H,C₁₋₆ alkyl, C₂₋₆ alkenyl, CF₃, aryl, and —CN; R is selected from H, C₁₋₄alkyl, and C₂₋₄ alkenyl; and, n is selected from 1 and
 2. 5. A compoundof claim 2, wherein: X and Y are independently selected from H, halogen,C₁₋₆ alkyl, NO₂, CF₃, NR₂, OR, —CN, (CH₂)_(m)C(NH)NH₂, (CH₂)_(m)CO₂R,O(CH₂)_(n)CO₂R, OCH₂CHCHCO₂R, CH₂O(CH₂)_(n)CO₂R, CH₂OCH₂CH═CHCO₂R,O(CH₂)_(n)PO(OR)₂, CH₂O(CH₂)_(n)PO(OR)₂, NR^(a)(CH₂)_(n)CO₂R,NR^(a)(CH₂)_(n)PO(OR)₂, NR^(a)CH₂CH═CHCO₂R, NR^(a)SO₂CH₃,NR^(a)CO(CH₂)_(n)CO₂R, O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄(CH₂)_(n)CO₂R,CH₂O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄(CH₂)_(n)CONH₂, O(CH₂)_(n)C₆H₄-tetrazole,CH₂O(CH₂)_(n)C₆H₄CONH₂, CH₂O(CH₂)_(n)C₆H₄-tetrazole,O(CH₂)_(n)C₆H₄(CH₂)_(n)-tetrazole, NR^(a)(CH₂)_(n)C₆H₄CO₂R,CH₂NR^(a)(CH₂)_(n)C₆H₄CO₂R, NR^(a)(CH₂)_(n)C₆H₄CONH₂,CH₂NR^(a)(CH₂)_(n)C₆H₄CONH₂, NR^(a)(CH₂)_(n)C₆H₄-tetrazole,CH₂NR^(a)(CH₂)_(n)C₆H₄-tetrazole, CONR₂, (CH₂)_(n)CONR₂,O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONH₂, NR^(a)(CH₂)_(n)CONR₂,OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂, NR^(a)CH₂CH═CHCONR₂, -tetrazole,O(CH₂CH₂O)_(p)R, NR^(a)(CH₂CH₂O)_(p)R, and SO₂NR^(a)CH_(3;) providedthat at least one of X and Y is other than H, halogen, C₁₋₆ alkyl, —CN,NO₂, CF₃, and OR; X′ and Y′ are independently selected from H, halogen,C₁₋₆ alkyl, —CN, NO₂, NR₂, and OR; Z is selected from H, C₁₋₄ alkyl, andaryl; Q is selected from N and CH; V is selected from H, C₁₋₄ alkyl, andaryl; R is selected from H, C₁₋₄ alkyl, and C₂₋₄ alkenyl; and, n isselected from 1 and
 2. 6. A compound of claim 2, wherein: X and Y areindependently selected from H, halogen, C₁₋₄ alkyl, —CN, NO₂, NR₂, andOR; X′ and Y′ are independently selected from H, halogen, C₁₋₆ alkyl,—CN, NO₂, CF₃, NR₂, OR, CO₂R, (CH₂)_(n)CO₂R, (CH₂)_(m)C(NH)NH₂,O(CH₂)_(n)CO₂R, OCH₂CHCHCO₂R, CH₂O(CH₂)_(n)CO₂R, CH₂OCH₂CH═CHCO₂R,O(CH₂)_(n)PO(OR)_(2,)CH₂O(CH₂)_(n)PO(OR)₂, NR^(a)(CH₂)_(n)CO₂R,NR^(a)(CH₂)_(n)PO(OR)₂, NR^(a)CH₂CH═CHCO₂R, NR^(a)SO₂CH₃,NR^(a)CO(CH₂)_(n)CO₂R, O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄(CH₂)_(n)CO₂R,CH₂O(CH₂)_(n)C₆H₄CO₂R, O(CH₂)_(n)C₆H₄CONH₂,O(CH₂)_(n)C₆H₄(CH₂)_(n)CONH₂, O(CH₂)_(n)C₆H₄-tetrazole,CH₂O(CH₂)_(n)C₆H₄CONH₂, CH₂O(CH₂)_(n)C₆H₄-tetrazole,O(CH₂)_(n)C₆H₄(CH₂)_(n)-tetrazole, NR^(a)(CH₂)_(n)C₆H₄CO₂R,CH₂NR^(a)(CH₂)_(n)C₆H₄CO₂R, NR^(a)(CH₂)_(n)C₆H₄CONH₂,CH₂NR^(a)(CH₂)_(n)C₆H₄CONH₂, NR^(a)(CH₂)_(n)C₆H₄-tetrazole,CH₂NR^(a)(CH₂)_(n)C₆H₄-tetrazole, CONR₂, (CH₂)_(n)CONR₂,O(CH₂)_(n)CONR₂, CH₂O(CH₂)_(n)CONH₂, NR^(a)(CH₂)_(n)CONR₂,OCH₂CH═CHCONR₂, CH₂OCH₂CH═CHCONR₂, NR^(a)CH₂CH═CHCONR₂, -tetrazole,O(CH₂CH₂O)_(p)R, NR^(a)(CH₂CH₂O)_(p)R, and SO₂NR^(a)CH₃; provided thatat least one of X′ and Y′ is other than halogen, C₁₋₄ alkyl, —CN, NO₂,and OR; Z is selected from H, C₁₋₄ alkyl, and aryl; Q is selected from Nand CH; V is selected from H, C₁₋₄ alkyl, and aryl; R is selected fromH, C₁₋₄ alkyl, and C₂₋₄ alkenyl; n is selected from 1 and 2; and, p isselected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and
 12. 7. A compound ofclaim 2, wherein: X and Y are independently selected from H, CF₃,halogen, C₁₋₄ alkyl, —CN, NO₂, NR₂, and OR; X′ and Y′ are independentlyselected from H, CF₃, halogen, C₁₋₄ alkyl, —CN, NO₂, NR₂, and OR; Z isselected from H, C₁₋₄ alkyl, and aryl; Q is selected from N and CH; V isselected from (CH₂)_(m)CO₂R, (CH₂)_(m)CONR₂, (CH₂)_(m)C(NH)NH₂,(CH₂)_(m)-tetrazole, (CH₂)_(m)CONR^(a)CH(A)₄CH₂)_(m)CO₂R,(CH₂)_(m)CONR^(a)(CH₂)_(m)-phenyl-(CH₂)_(m)CO₂R,(CH₂)_(m)CONR^(a)(CH₂)_(m)-phenyl-(CH₂)_(m)-tetrazole,CH₂O(CH₂)_(n)CO₂R, CH₂NR^(a)(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CONH₂,CH₂NR^(a)(CH₂)_(n)CONH₂, and CH₂O(CH₂)_(n)tetrazole; A is selected fromH, C₁₋₄ alkyl, and (CH₂)_(m)-aryl, wherein each aryl is optionallysubstituted with 0-1 groups selected from CF₃, halogen, C₁₋₄ alkyl, —CN,CONR₂, NO₂, NR₂, and OR; R is selected from H, C₁₋₄ alkyl, and C₂₋₄alkenyl; m is selected from 0,1, and 2; and, n is selected from 1 and 2.8. A compound of claim 1, wherein the compound is selected from: TABLE C

Number Z Y C-1 3-CO₂Et Cl C-2 4-CO₂Et Cl C-3 3-CONH₂ Cl C-4 4-CO₂Et OCH₃

TABLE D

Number Q” n D-1 OEt 2

TABLE E

Number Z E-1 4-CO₂Et E-2 4-CONH₂

or a pharmaceutically acceptable salt thereof.
 9. A compound of claim 1,wherein the compound is selected from the compounds of Table 1a, 1b, 1c,2a, 2b, -3a, 3b -and-4, or stereoisomer or a pharmaceutically acceptablesalt thereof: TABLE 1a Z (position on Ex. # Y ring) O n 1 Cl 2-CO₂Et N 12 Cl 2-CO₂H N 1 3 Cl 2-CH₂CO₂Et N 1 4 Cl 2-CH₂CO₂H N 1 5 CH₃ 2-CO₂Et N 16 CH₃ 2-CO₂H N 1 7 CH₃ 2-CH₂CO₂Et N 1 8 CH₃ 2-CH₂CO₂H N 1 9 OCH₃ 2-CO₂EtN 1 10 OCH₃ 2-CO₂H N 1 11 OCH₃ 2-CH₂CO₂Et N 1 12 OCH₃ 2-CH₂CO₂H N 1 13CH(CH₃)₂ 2-CO₂Et N 1 14 CH(CH₃)₂ 2-CO₂H N 1 15 CH(CH₃)₂ 2-CH₂CO₂Et N 116 CH(CH₃)₂ 2-CH₂CO₂H N 1 17 Cl 2-CO₂Et N 2 18 Cl 2-CO₂H N 2 19 Cl2-CH₂CO₂Et N 2 20 Cl 2-CH₂CO₂H N 2 21 CH₃ 2-CO₂Et N 2 22 CH₃ 2-CO₂H N 223 CH₃ 2-CH₂CO₂Et N 2 24 CH₃ 2-CH₂CO₂H N 2 25 OCH₃ 2-CO₂Et N 2 26 OCH₃2-CO₂H N 2 27 OCH₃ 2-CH₂CO₂Et N 2 28 OCH₃ 2-CH₂CO₂H N 2 29 CH(CH₃)₂2-CO₂Et N 2 30 CH(CH₃)₃ 2-CO₂H N 2 31 CH(CH₃)₂ 2-CH₂CO₂Et N 2 32CH(CH₃)₂ 2-CH₂CO₂H N 2 33 Cl 3-CO₂Et N 1 34 Cl 3-CO₂H N 1 35 Cl3-CH₂CO₂Et N 1 36 Cl 3-CH₂CO₂H N 1 37 CH₃ 3-CO₂Et N 1 38 CH₃ 3-CO₂H N 139 CH₃ 3-CH₂CO₂Et N 1 40 CH₃ 3-CH₂CO₂H N 1 41 OCH₃ 3-CO₂Et N 1 42 OCH₃3-CO₂H N 1 43 OCH₃ 3-CH₂CO₂Et N 1 44 OCH₃ 3-CH₂CO₂H N 1 45 CH(CH₃)₂3-CO₂Et N 1 46 CH(CH₃)₂ 3-COH N 1 47 CH(CH₃)₂ 3-CH₂CO₂Et N 1 48 CH(CH₃)₂3-CH₂CO₂H N 1 49 Cl 3-CO₂Et N 2 50 Cl 3-CO₂H N 2 51 Cl 3-CH₂CO₂Et N 2 52Cl 3-CH₂CO₂H N 2 53 CH₃ 3-CO₂Et N 2 54 CH₃ 3-CO₂H N 2 55 CH₃ 3-CH₂CO₂EtN 2 56 Cl₃ 3-CH₂CO₂H N 2 57 OCH₃ 3-CO₂Et N 2 58 OCH₃ 3-CO₂H N 2 59 OCH₃3-CH₂CO₂Et N 2 60 OCH₃ 3-CH₂CO₂H N 2 61 CH(CH₃)₂ 3-CO₂Et N 2 62 CH(CH₃)₂3-CO₂H N 2 63 CH(CH₃)₂ 3-CH₂CO₂Et N 2 64 CH(CH₃)₂ 3-CH₂CO₂H N 2 65 Cl4-CO₂Et N 2 66 Cl 4-CO₂H N 2 67 Cl 4-CH₂CO₂Et N 2 68 Cl 4-CH₂CO₂H N 2 69Cl₃ 4-CO₂Et N 2 70 CH₃ 4-CO₂H N 2 71 CH₃ 4-CH₂CO₂Et N 2 72 CH₃ 4-CH₂CO₂HN 2 73 OCH₃ 4-CO₂Et N 2 74 OCH₃ 4-CO₂H N 2 75 OCH₃ 4-CH₂CO₂Et N 2 76OCH₃ 4-CH₂CO₂H N 2 77 CH(CH₃)₂ 4-CO₂Et N 2 78 CH(CH₃)₂ 4-CO₂H N 2 79CH(CH₃)₂ 4-CH₂CO₂Et N 2 80 CH(CH₃)₂ 4-CH₂CO₂H N 2 81 Cl 1-CO₂Et C 1 82Cl 1-CO₂H C 1 83 Cl 1-CH₂CO₂Et C 1 84 Cl 1-CH₂CO₂H C 1 85 Cl₃ 1-CO₂Et C1 86 CH₃ 1-CO₂H C 1 87 CH₃ 1-CH₂CO₂Et C 1 88 CH₃ 1-CH₂CO₂H C 1 89 OCH₃1-CO₂Et C 1 90 OCH₃ 1-CO₂H C 1 91 OCH₃ 1-CH₂CO₂Et C 1 92 OCH₃ 1-CH₂CO₂HC 1 93 CH(CH₃)₂ 1-CO₂Et C 1 94 CH(CH₃)₂ 1-CO₂H C 1 95 CH(CH₃)₂1-CH₂CO₂Et C 1 96 CH(CH₃)₂ 1-CH₂CO₂H C 1 97 Cl 1-CO₂Et C 2 98 Cl 1-CO₂HC 2 99 Cl 1-CH₂CO₂Et C 2 100 Cl 1-CH₂CO₂H C 2 101 Cl₃ 1-CO₂Et C 2 102CH₃ 1-CO₂H C 2 103 CH₃ 1-CH₂CO₂Et C 2 104 CH₃ 2-CH₂CO₂H C 2 105 OCH₃2-CO₂Et C 2 105 OCH₃ 1-CO₂H C 2 107 OCH₃ 1-CH₂CO₂Et C 2 108 OCH₃1-CH₂CO₂H C 2 109 CH(CH₃)₂ 1-CO₂Et C 2 110 CH(CH₃)₂ 1-CO₂H C 2 111CH(CH₃)₂ 1-CH₂CO₂Et C 2 112 CH(CH₃)₂ 1-CH₂CO₂H C 2 113 Cl 2-CO₂Et CH 1114 Cl 2-CO₂H CH 1 115 Cl 2-CH₂CO₂Et CH 1 116 Cl 2-CH₂CO₂H CH 1 117 CH₃2-CO₂Et CH 1 118 CH₃ 2-CO₂H CH 1 119 CH₃ 2-CH₂CO₂Et CH 1 120 CH₃2-CH₂CO₂H CH 1 121 OCH₃ 2-CO₂Et CH 1 122 OCH₃ 2-CO₂H CH 1 123 OCH₃2-CH₂CO₂Et CH 1 124 OCH₃ 2-CH₂CO₂H CH 1 125 CH(CH₃)₂ 2-CO₂Et CH 1 126CH(CH₃)₂ 2-CO₂H CH 1 127 CH(CH₃)₂ 2-CH₂CO₂Et CH 1 128 CH(CH₃)₂ 2-CH₂CO₂HCH 1 129 Cl 2-CO₂Et CH 2 130 Cl 2-CO₂H CH 2 131 Cl 2-CH₂CO₂Et CH 2 132Cl 2-CH₂CO₂H CH 2 133 CH₃ 2-CO₂Et CH 2 134 CH₃ 2-CO₂H CH 2 135 CH₃2-CH₂CO₂Et CH 2 136 CH₃ 2-CH₂CO₂H CH 2 137 OCH₃ 2-CO₂Et CH 2 138 OCH₃2-CO₂H CH 2 139 OCH₃ 2-CH₂CO₂Et CH 2 140 OCH₃ 2-CH₂CO₂H CH 2 141CH(CH₃)₂ 2-CO₂Et CH 2 142 CH(CH₃)₂ 2-CO₂H CH 2 143 CH(CH₃)₂ 2-CH₂CO₂EtCH 2 144 CH(CH₃)₂ 2-CH₂CO₂H CH 2

TABLE 1b

Ex. # Y Z (position on ring) Q n 1 Cl 2-CH₂OCH₂CO₂Et N 1 2 Cl2-CH₂OCH₂CO₂H N 1 3 Cl 2- N 1 CH₂O(CH₂)₃PO(OEt)₂ 4 Cl2-CH₂O(CH₂)₃PO(OH)₂ N 1 5 CH₃ 2-CH₂OCH₂CO₂Et N 1 6 CH₃ 2-CH₂OCH₂CO₂H N 17 CH₃ 2- N 1 CH₂O(CH₂)₃PO(OEt)₂ 8 CH₃ 2-CH₂O(CH₂)₃PO(OH)₂ N 1 9 OCH₃2-CH₂OCH₂CO₂Et N 1 10 OCH₃ 2-CH₂OCH₂CO₂H N 1 11 OCH₃ 2- N 1CH₂O(CH₂)₃PO(OEt)₂ 12 OCH₃ 2-CH₂O(CH₂)₃PO(OH)₂ N 1 13 CH(CH₃)₂2-CH₂OCH₂CO₂Et N 1 14 CH(CH₃)₂ 2-CH₂OCH₂CO₂H N 1 15 CH(CH₃)₂ 2- N 1CH₂O(CH₂)₃PO(OEt)₂ 16 CH(CH₃)₂ 2-CH₂O(CH₂)₃PO(OH)₂ N 1 17 Cl2-CH₂OCH₂CO₂Et N 2 18 Cl 2-CH₂OCH₂CO₂H N 2 19 Cl 2- N 2CH₂O(CH₂)₃PO(OEt)₂ 20 Cl 2-CH₂O(CH₂)₃PO(OH)₂ N 2 21 CH₃ 2-CH₂OCH₂CO₂Et N2 22 CH₃ 2-CH₂OCH₂CO₂H N 2 23 CH₃ 2- N 2 CH₂O(CH₂)₃PO(OEt)₂ 24 CH₃2-CH₂O(CH₂)₃PO(OH)₂ N 2 25 OCH₃ 2-CH₂OCH₂CO₂Et N 2 26 OCH₃ 2-CH₂OCH₂CO₂HN 2 27 OCH₃ 2- N 2 CH₂O(CH₂)₃PO(OEt)₂ 28 OCH₃ 2-CH₂O(CH₂)₃PO(OH)₂ N 2 29CH(CH₃)₂ 2-CH₂OCH₂CO₂Et N 2 30 CH(CH₃)₂ 2-CH₂OCH₂CO₂H N 2 31 CH(CH₃)₂ 2-N 2 CH₂O(CH₂)₃PO(OEt)₂ 32 CH(CH₃)₂ 2-CH₂O(CH₂)₃PO(OH)₂ N 2 33 Cl3-CH₂OCH₂CO₂Et N 1 34 Cl 3-CH₂OCH₂CO₂H N 1 35 Cl 3- N 1CH₂O(CH₂)₃PO(OEt)₂ 36 Cl 3-CH₂O(CH₂)₃PO(OH)₂ N 1 37 CH₃ 3-CH₂OCH₂CO₂Et N1 38 CH₃ 3-CH₂OCH₂CO₂H N 1 39 CH₃ 3- N 1 CH₂O(CH₂)₃PO(OEt)₂ 40 CH₃3-CH₂O(CH₂)₃PO(OH)₂ N 1 41 OCH₃ 3-CH₂OCH₂CO₂Et N 1 42 OCH₃ 3-CH₂OCH₂CO₂HN 1 43 OCH₃ 3- N 1 CH₂O(CH₂)₃PO(OEt)₂ 44 OCH₃ 3-CH₂O(CH₂)₃PO(OH)₂ N 1 45CH(CH₃)₂ 3-CH₂OCH₂CO₂Et N 1 46 CH(CH₃)₂ 3-CH₂OCH₂CO₂H N 1 47 CH(CH₃)₂ 3-N 1 CH₂O(CH₂)₃PO(OEt)₂ 48 CH(CH₃)₂ 3-CH₂O(CH₂)₃PO(OH)₂ N 1 49 Cl3-CH₂OCH₂CO₂Et N 2 50 Cl 3-CH₂OCH₂CO₂H N 2 51 Cl 3- N 2CH₂O(CH₂)₃PO(OEt)₂ 52 Cl 3-CH₂O(CH₂)₃PO(OH)₂ N 2 53 CH₃ 3-CH₂OCH₂CO₂Et N2 54 CH₃ 3-CH₂OCH₂CO₂H N 2 55 CH₃ 3- N 2 CH₂O(CH₂)₃PO(OEt)₂ 56 CH₃3-CH₂O(CH₂)₃PO(OH)₂ N 2 57 OCH₃ 3-CH₂OCH₂CO₂Et N 2 58 OCH₃ 3-CH₂OCH₂CO₂HN 2 59 OCH₃ 3- N 2 CH₂O(CH₂)₃PO(OEt)₂ 60 OCH₃ 3-CH₂O(CH₂)₃PO(OH)₂ N 2 61CH(CH₃)₂ 3-CH₂OCH₂CO₂Et N 2 62 CH(CH₃)₂ 3-CH₂OCH₂CO₂H N 2 63 CH(CH₃)₂ 3-N 2 CH₂O(CH₂)₃PO(OEt)₂ 64 CH(CH₃)₂ 3-CH₂O(CH₂)₃PO(OH)₂ N 2 65 Cl4-CH₂OCH₂CO₂Et N 2 66 Cl 4-CH₂OCH₂CO₂H N 2 67 Cl 4- N 2CH₂O(CH₂)₃PO(OEt)₂ 68 Cl 4-CH₂O(CH₂)₃PO(OH)₂ N 2 69 CH₃ 4-CH₂OCH₂CO₂Et N2 70 CH₃ 4-CH₂OCH₂CO₂H N 2 71 CH₃ 4- N 2 CH₂O(CH₂)₃PO(OEt)₂ 72 CH₃4-CH₂O(CH₂)₃PO(OH)₂ N 2 73 OCH₃ 4-CH₂OCH₂CO₂Et N 2 74 OCH₃ 4-CH₂OCH₂CO₂HN 2 75 OCH₃ 4- N 2 CH₂O(CH₂)₃PO(OEt)₂ 76 OCH₃ 4-CH₂O(CH₂)₃PO(OH)₂ N 2 77CH(CH₃)₂ 4-CH₂OCH₂CO₂Et N 2 78 CH(CH₃)₂ 4-CH₂OCH₂CO₂H N 2 79 CH(CH₃)₂ 4-N 2 CH₂O(CH₂)₃PO(OEt)₂ 80 CH(CH₃)₂ 4-CH₂O(CH₂)₃PO(OH)₂ N 2 81 Cl2-CH₂OCH₂CO₂Et CH 1 82 Cl 2-CH₂OCH₂CO₂H CH 1 83 Cl 2- CH 1CH₂O(CH₂)₃PO(OEt)₂ 84 Cl 2-CH₂O(CH₂)₃PO(OH)₂ CH 1 85 CH₃ 2-CH₂OCH₂CO₂EtCH 1 86 CH₃ 2-CH₂OCH₂CO₂H CH 1 87 CH₃ 2- CH 1 CH₂O(CH₂)₃PO(OEt)₂ 88 CH₃2-CH₂O(CH₂)₃PO(OH)₂ CH 1 89 OCH₃ 2-CH₂OCH₂CO₂Et CH 1 90 OCH₃2-CH₂OCH₂CO₂H CH 1 91 OCH₃ 2- CH 1 CH₂O(CH₂)₃PO(OEt)₂ 92 OCH₃2-CH₂O(CH₂)₃PO(OH)₂ CH 1 93 CH(CH₃)₂ 2-CH₂OCH₂CO₂Et CH 1 94 CH(CH₃)₂2-CH₂OCH₂CO₂H CH 1 95 CH(CH₃)₂ 2- CH 1 CH₂O(CH₂)₃PO(OEt)₂ 96 CH(CH₃)₂2-CH₂O(CH₂)₃PO(OH)₂ CH 1 97 Cl 2-CH₂OCH₂CO₂Et CH 2 98 Cl 2-CH₂OCH₂CO₂HCH 2 99 Cl 2- CH 2 CH₂O(CH₂)₃PO(OEt)₂ 100 Cl 2-CH₂O(CH₂)₃PO(OH)₂ CH 2101 CH₃ 2-CH₂OCH₂CO₂Et CH 2 102 CH₃ 2-CH₂OCH₂CO₂H CH 2 103 CH₃ 2- CH 2CH₂O(CH₂)₃PO(OEt)₂ 104 CH₃ 2-CH₂O(CH₂)₃PO(OH)₂ CH 2 105 OCH₃2-CH₂OCH₂CO₂Et CH 2 105 OCH₃ 2-CH₂OCH₂CO₂H CH 2 107 OCH₃ 2- CH 2CH₂O(CH₂)₃PO(OEt)₂ 108 OCH₃ 2-CH₂O(CH₂)₃PO(OH)₂ CH 2 109 CH(CH₃)₂2-CH₂OCH₂CO₂Et CH 2 110 CH(CH₃)₂ 2-CH₂OCH₂CO₂H CH 2 111 CH(CH₃)₂ 2- CH 2CH₂O(CH₂)₃PO(OEt)₂ 112 CH(CH₃)₂ 2-CH₂O(CH₂)₃PO(OH)₂ CH 2 113 Cl1-CH₂OCH₂CO₂Et C 1 114 Cl 1CH₂OCH₂CO₂H C 1 115 Cl 1- C 1CH₂O(CH₂)₃PO(OEt)₂ 116 Cl 1-CH₂O(CH₂)₃PO(OH)₂ C 1 117 CH₃ 1-CH₂OCH₂CO₂EtC 1 118 CH₃ 1-CH₂OCH₂CO₂H C 1 119 CH₃ 1- C 1 CH₂O(CH₂)₃PO(OEt)₂ 120 CH₃1-CH₂O(CH₂)₃PO(OH)₂ C 1 121 OCH₃ 1-CH₂OCH₂CO₂Et C 1 122 OCH₃1-CH₂OCH₂CO₂H C 1 123 OCH₃ 1- C 1 CH₂O(CH₂)₃PO(OEt)₂ 124 OCH₃1-CH₂O(CH₂)₃PO(OH)₂ C 1 125 CH(CH₃)₂ 1-CH₂OCH₂CO₂Et C 1 126 CH(CH₃)₂1-CH₂OCH₂CO₂H C 1 127 CH(CH₃)₂ 1- C 1 CH₂O(CH₂)₃PO(OEt)₂ 128 CH(CH₃)₂1-CH₂O(CH₂)₃PO(OH)₂ C 1 129 Cl 3-CH₂OCH₂CO₂Et CH 2 130 Cl 3-CH₂OCH₂CO₂HCH 2 131 Cl 3- CH 2 CH₂O(CH₂)₃PO(OEt)₂ 132 Cl 3-CH₂O(CH₂)₃PO(OH)₂ CH 2133 CH₃ 3-CH₂OCH₂CO₂Et CH 2 134 CH₃ 3-CH₂OCH₂CO₂H CH 2 135 CH₃ 3- CH 2CH₂O(CH₂)₃PO(OEt)₂ 136 CH₃ 3-CH₂O(CH₂)₃PO(OH)₂ CH 2 137 OCH₃3-CH₂OCH₂CO₂Et CH 2 138 OCH₃ 3-CH₂OCH₂CO₂H CH 2 139 OCH₃ 3- CH 2CH₂O(CH₂)₃PO(OEt)₂ 140 OCH₃ 3-CH₂O(CH₂)₃PO(OH)₂ CH 2 141 CH(CH₃)₂3-CH₂OCH₂CO₂Et CH 2 142 CH(CH₃)₂ 3-CH₂OCH₂CO₂H CH 2 143 CH(CH₃)₂ 3- CH 2CH₂O(CH₂)₃PO(OEt)₂ 144 CH(CH₃)₂ 3-CH₂O(CH₂)₃PO(OH)₂ CH 2

TABLE 1c

Ex. # Y Z (position on ring) Q n 1 Cl 2-CONH₂ N 1 2 Cl 2-CH₂OCH₂CONH₂ N1 3 Cl 2-CH₂CONH₂ N 1 4 Cl 2-CH₂OCH₂CH═CHCONH₂ N 1 5 CH₃ 2-CONH₂ N 1 6CH₃ 2-CH₂OCH₂CONH₂ N 1 7 CH₃ 2-CH₂CONH₂ N 1 8 CH₃ 2-CH₂OCH₂CH═CHCONH₂ N1 9 OCH₃ 2-CONH₂ N 1 10 OCH₃ 2-CH₂OCH₂CONH₂ N 1 11 OCH₃ 2-CH₂CONH₂ N 112 OCH₃ 2-CH₂OCH₂CH═CHCONH₂ N 1 13 CH(CH₃)₂ 2-CONH₂ N 1 14 CH(CH₃)₂2-CH₂OCH₂CONH₂ N 1 15 CH(CH₃)₂ 2-CH₂CONH₂ N 1 16 CH(CH₃)₂2-CH₂OCH₂CH═CHCONH₂ N 1 17 Cl 2-CONH₂ N 2 18 Cl 2-CH₂OCH₂CONH₂ N 2 19 Cl2-CH₂CONH₂ N 2 20 Cl 2-CH₂OCH₂CH═CHCONH₂ N 2 21 CH₃ 2-CONH₂ N 2 22 CH₃2-CH₂OCH₂CONH₂ N 2 23 CH₃ 2-CH₂CONH₂ N 2 24 CH₃ 2-CH₂OCH₂CH═CHCONH₂ N 225 OCH₃ 2-CONH₂ N 2 26 OCH₃ 2-CH₂OCH₂CONH₂ N 2 27 OCH₃ 2-CH₂CONH₂ N 2 28OCH₃ 2-CH₂OCH₂CH═CHCONH₂ N 2 29 CH(CH₃)₂ 2-CONH₂ N 2 30 CH(CH₃)₂2-CH₂OCH₂CONH₂ N 2 31 CH(CH₃)₂ 2-CH₂CONH₂ N 2 32 CH(CH₃)₂2-CH₂OCH₂CH═CHCONH₂ N 2 33 Cl 3-CONH₂ N 1 34 Cl 3-CH₂OCH₂CONH₂ N 1 35 Cl3-CH₂CONH₂ N 1 36 Cl 3-CH₂OCH₂CH═CHCONH₂ N 1 37 CH₃ 3-CONH₂ N 1 38 CH₃3-CH₂OCH₂CONH₂ N 1 39 CH₃ 3-CH₂CONH₂ N 1 40 CH₃ 3-CH₂OCH₂CH═CHCONH₂ N 141 OCH₃ 3-CONH₂ N 1 42 OCH₃ 3-CH₂OCH₂CONH₂ N 1 43 OCH₃ 3-CH₂CONH₂ N 1 44OCH₃ 3-CH₂OCH₂CH═CHCONH₂ N 1 45 CH(CH₃)₂ 3-CONH₂ N 1 4 CH(CH₃)₂3-CH₂OCH₂CONH₂ N 1 47 CH(CH₃)₂ 3-CH₂CONH₂ N 1 48 CH(CH₃)₂3-CH₂OCH₂CH═CHCONH₂ N 1 49 Cl 3-CONH₂ N 2 50 Cl 3-CH₂OCH₂CONH₂ N 2 51 Cl3-CH₂CONH₂ N 2 52 Cl 3-CH₂OCH₂CH═CHCONH₂ N 2 53 CH₃ 3-CONH₂ N 2 54 CH₃3-CH₂OCH₂CONH₂ N 2 55 CH₃ 3-CH₂CONH₂ N 2 56 CH₃ 3-CH₂OCH₂CH═CHCONH₂ N 257 OCH₃ 3-CONH₂ N 2 58 OCH₃ 3-CH₂OCH₂CONH₂ N 2 59 OCH₃ 3-CH₂CONH₂ N 2 60OCH₃ 3-CH₂OCH₂CH═CHCONH₂ N 2 61 CH(CH₃)₂ 3-CONH₂ N 2 62 CH(CH₃)₂3-CH₂OCH₂CONH₂ N 2 63 CH(CH₃)₂ 3-CH₂CONH₂ N 2 64 CH(CH₃)₂3-CH₂OCH₂CH═CHCONH₂ N 2 65 Cl 4-CONH₂ N 2 66 Cl 4-CH₂OCH₂CONH₂ N 2 67 Cl4-CH₂CONH₂ N 2 68 Cl 4-CH₂OCH₂CH═CHCONH₂ N 2 69 CH₃ 4-CONH₂ N 2 70 CH₃4-CH₂OCH₂CONH₂ N 2 71 CH₃ 4-CH₂CONH₂ N 2 72 CH₃ 4-CH₂OCH₂CH═CHCONH₂ N 273 OCH₃ 4-CONH₂ N 2 74 OCH₃ 4-CH₂OCH₂CONH₂ N 2 75 OCH₃ 4-CH₂CONH₂ N 2 76OCH₃ 4-CH₂OCH₂CH═CHCONH₂ N 2 77 CH(CH₃)₂ 4-CONH₂ N 2 78 CH(CH₃)₂4-CH₂OCH₂CONH₂ N 2 79 CH(CH₃)₂ 4-CH₂CONH₂ N 2 80 CH(CH₃)₂4-CH₂OCH₂CH═CHCONH₂ N 2 81 Cl 1-CONH₂ C 1 82 Cl 1-CH₂OCH₂CONH₂ C 1 83 Cl1-CH₂CONH₂ C 1 84 CH₃ 1-CONH₂ C 1 85 CH₃ 1-CH₂OCH₂CONH₂ C 1 86 CH₃1-CH₂CONH₂ C 1 87 OCH₃ 1-CONH₂ C 1 88 OCH₃ 1-CH₂OCH₂CONH₂ C 1 89 OCH₃1-CH₂CONH₂ C 1 90 CH(CH₃)₂ 1-CONH₂ C 1 91 CH(CH₃)₂ 1-CH₂OCH₂CONH₂ C 1 92CH(CH₃)₂ 1-CH₂CONH₂ C 1 93 Cl 1-CONH₂ C 2 94 Cl 1-CH₂OCH₂CONH₂ C 2 95 Cl1-CH₂CONH₂ C 2 96 CH₃ 1-CONH₂ C 2 97 CH₃ 1-CH₂OCH₂CONH₂ C 2 98 CH₃1-CH₂CONH₂ C 2 99 OCH₃ 1-CONH₂ C 2 100 OCH₃ 1-CH₂OCH₂CONH₂ C 2 101 OCH₃1-CH₂CONH₂ C 2 102 CH(CH₃)₂ 1-CONH₂ C 2 103 CH(CH₃)₂ 1-CH₂OCH₂CONH₂ C 2104 CH(CH₃)₂ 1-CH₂CONH₂ C 2 105 Cl 2-CONH₂ CH 1 105 Cl 2-CH₂OCH₂CONH₂ CH1 107 Cl 2-CH₂CONH₂ CH 1 108 Cl 2-CH₂OCH₂CH═CHCONH₂ CH 1 109 CH₃ 2-CONH₂CH 1 110 CH₃ 2-CH₂OCH₂CONH₂ CH 1 111 CH₃ 2-CH₂CONH₂ CH 1 112 CH₃2-CH₂OCH₂CH═CHCONH₂ CH 1 113 OCH₃ 2-CONH₂ CH 1 114 OCH₃ 2-CH₂OCH₂CONH₂CH 1 115 OCH₃ 2-CH₂CONH₂ CH 1 116 OCH₃ 2-CH₂OCH₂CH═CHCONH₂ CH 1 117CH(CH₃)₂ 2-CONH₂ CH 1 118 CH(CH₃)₂ 2-CH₂OCH₂CONH₂ CH 1 119 CH(CH₃)₂2-CH₂CONH₂ CH 1 120 CH(CH₃)₂ 2-CH₂OCH₂CH═CHCONH₂ CH 1 121 Cl 2-CONH₂ CH2 122 Cl 2-CH₂OCH₂CONH₂ CH 2 123 Cl 2-CH₂CONH₂ CH 2 124 Cl2-CH₂OCH₂CH═CHCONH₂ CH 2 125 CH₃ 2-CONH₂ CH 2 126 CH₃ 2-CH₂OCH₂CONH₂ CH2 127 CH₃ 2-CH₂CONH₂ CH 2 128 CH₃ 2-CH₂OCH₂CH═CHCONH₂ CH 2 129 OCH₃2-CONH₂ CH 2 130 OCH₃ 2-CH₂OCH₂CONH₂ CH 2 131 OCH₃ 2-CH₂CONH₂ CH 2 132OCH₃ 2-CH₂OCH₂CH═CHCONH₂ CH 2 133 CH(CH₃)₂ 2-CONH₂ CH 2 134 CH(CH₃)₂2-CH₂OCH₂CONH₂ CH 2 135 CH(CH₃)₂ 2-CH₂CONH₂ CH 2 136 CH(CH₃)₂2-CH₂OCH₂CH═CHCONH₂ CH 2 137 Cl 3-CONH₂ CH 1 138 Cl 3-CH₂OCH₂CONH₂ CH 1139 Cl 3-CH₂CONH₂ CH 1 140 Cl 3-CH₂OCH₂CH═CHCONH₂ CH 1 141 CH₃ 3-CONH₂CH 1 142 CH₃ 3-CH₂OCH₂CONH₂ CH 1 143 CH₃ 3-CH₂CONH₂ CH 1 144 CH₃3-CH₂OCH₂CH═CHCONH₂ CH 1 145 OCH₃ 3-CONH₂ CH 1 146 OCH₃ 3-CH₂OCH₂CONH₂CH 1 147 OCH₃ 3-CH₂CONH₂ CH 1 148 OCH₃ 3-CH₂OCH₂CH═CHCONH₂ CH 1 149CH(CH₃)₂ 3-CONH₂ CH 1 150 CH(CH₃)₂ 3-CH₂OCH₂CONH₂ CH 1 151 CH(CH₃)₂3-CH₂CONH₂ CH 1 153 CH(CH₃)₂ 3-CH₂OCH₂CH═CHCONH₂ CH 1 154 Cl 4-CONH₂ CH2 155 Cl 4-CH₂OCH₂CONH₂ CH 2 156 Cl 4-CH₂CONH₂ CH 2 157 Cl4-CH₂OCH₂CH═CHCONH₂ CH 2 158 CH₃ 4-CONH₂ CH 2 159 CH₃ 4-CH₂OCH₂CONH₂ CH2 160 CH₃ 4-CH₂CONH₂ CH 2 161 CH₃ 4-CH₂OCH₂CH═CHCONH₂ CH 2 162 OCH₃4-CONH₂ CH 2 163 OCH₃ 4-CH₂OCH₂CONH₂ CH 2 164 OCH₃ 4-CH₂CONH₂ CH 2 165OCH₃ 4-CH₂OCH₂CH═CHCONH₂ CH 2 166 CH(CH₃)₂ 4-CONH₂ CH 2 176 CH(CH₃)₂4-CH₂OCH₂CONH₂ CH 2 168 CH(CH₃)₂ 4-CH₂CONH₂ CH 2 169 CH(CH₃)₂4-CH₂OCH₂CH═CHCONH₂ CH 2 170 Cl 4-C(NH)NH₂ N 2 171 Cl 3-C(NH)NH₂ N 2 172Cl 2-C(NH)NH₂ N 1 173 Cl 3-C(NH)NH₂ N 1 174 OCH₃ 4-C(NH)NH₂ N 2 175 OCH₃3-C(NH)NH₂ N 2 176 OCH₃ 2-C(NH)NH₂ N 1 177 OCH₃ 3-C(NH)NH₂ N 1 178 CH₃4-C(NH)NH₂ N 2 179 CH₃ 3-C(NH)NH₂ N 2 180 CH₃ 2-C(NH)NH₂ N 1 181 CH₃3-C(NH)NH₂ N 1 182 CH(CH₃)₂ 4-C(NH)NH₂ N 2 183 CH(CH₃)₂ 3-C(NH)NH₂ N 2184 CH(CH₃)₂ 2-C(NH)NH₂ N 1 185 CH(CH₃)₂ 3-C(NH)NH₂ N 1

TABLE 2a

Ex. # X Y X′ 1 CO₂Et H H 2 CO₂H H H 3 CH₂CO₂Et H H 4 CH₂CO₂H H H 5OCH₂CO₂Et H H 6 OCH₂CO₂H H H 7 OCH₂CH₂CH₂PO(OEt)₂ H H 8OCH₂CH₂CH₂PO(OH)₂ H H 9 OCH₂C₆H₄CO₂Et H H 10 OCH₂C₆H₄CO₂H H H 11NHCH₂CO₂Et H H 12 NHCH₂CO₂H H H 13 NHCH₂CH₂CH₂PO(OEt)₂ H H 14NHCH₂CH₂CH₂PO(OH)₂ H H 15 NHCH₂C₆H₄CO₂Et H H 16 NHCH₂C₆H₄CO₂H H H 17NHCOCH₂CH₂CO₂Et H H 18 NHCOCH₂CH₂CO₂H H H 19 NHSO₂CH₃ H H 20NHCH₂CH═CHCO₂Et H H 21 NHCH₂CH═CHCO₂H H H 22 CONH₂ H H 23 CH₂CONH₂ H H24 OCH₂CONH₂ H H 25 CN₄H H H 26 H CO₂Et H 27 H CO₂H H 28 H CH₂CO₂Et H 29H CH₂CO₂H H 30 H OCH₂CO₂Et H 31 H OCH₂CO₂H H 32 H OCH₂CH₂CH₂PO(OEt)₂ H33 H OCH₂CH₂CH₂PO(OH)₂ H 34 H OCH₂C₆H₄CO₂Et H 35 H OCH₂C₆H₄CO₂H H 36 HNHCH₂CO₂Et H 37 H NHCH₂CO₂H H 38 H NHCH₂CH₂CH₂PO(OEt)₂ H 39 HNHCH₂CH₂CH₂PO(OH)₂ H 40 H NHCH₂C₆H₄CO₂Et H 41 H NHCH₂C₆H₄CO₂H H 42 HNHCOCH₂CH₂CO₂Et H 43 H NHCOCH₂CH₂CO₂H H 44 H NHSO₂CH₃ H 45 HNHCH₂CH═CHCO₂Et H 46 H NHCH₂CH═CHCO₂H H 47 H CONH₂ H 48 H CH₂CONH₂ H 49H OCH₂CONH₂ H 50 H CN₄H H 51 CO₂Et H Cl 52 CO₂H H Cl 53 CH₂CO₂Et H Cl 54CH₂CO₂H H Cl 55 OCH₂CO₂Et H Cl 56 OCH₂CO₂H H Cl 57 OCH₂CH₂CH₂PO(OEt)₂ HCl 58 OCH₂CH₂CH₂PO(OH)₂ H Cl 59 OCH₂C₆H₄CO₂Et H Cl 60 OCH₂C₆H₄CO₂H H Cl61 NHCH₂CO₂Et H Cl 62 NHCH₂CO₂H H Cl 63 NHCH₂CH₂CH₂PO(OEt)₂ H Cl 64NHCH₂CH₂CH₂PO(OH)₂ H Cl 65 NHCH₂C₆H₄CO₂Et H Cl 66 NHCH₂C₆H₄CO₂H H Cl 67NHCOCH₂CH₂CO₂Et H Cl 68 NHCOCH₂CH₂CO₂H H Cl 69 NHSO₂CH₃ H Cl 70NHCH₂CH═CHCO₂Et H Cl 71 NHCH₂CH═CHCO₂H H Cl 72 CONH₂ H Cl 73 CH₂CONH₂ HCl 74 OCH₂CONH₂ H Cl 75 CN₄H H Cl 76 H CO₂Et Cl 77 H CO₂H Cl 78 HCH₂CO₂Et Cl 79 H CH₂CO₂H Cl 80 H OCH₂CO₂Et Cl 81 H OCH₂CO₂H Cl 82 HOCH₂CH₂CH₂PO(OEt)₂ Cl 83 H OCH₂CH₂CH₂PO(OH)₂ Cl 84 H OCH₂C₆H₄CO₂Et Cl 85H OCH₂C₆H₄CO₂H Cl 86 H NHCH₂CO₂Et Cl 87 H NHCH₂CO₂H Cl 88 HNHCH₂CH₂CH₂PO(OEt)₂ Cl 89 H NHCH₂CH₂CH₂PO(OH)₂ Cl 90 H NHCH₂C₆H₄CO₂Et Cl91 H NHCH₂C₆H₄CO₂H Cl 92 H NHCOCH₂CH₂CO₂Et Cl 93 H NHCOCH₂CH₂CO₂H Cl 94H NHSO₂CH₃ Cl 95 H NHCH₂CH═CHCO₂Et Cl 96 H NHCH₂CH═CHCO₂H Cl 97 H CONH₂Cl 98 H CH₂CONH₂ Cl 99 H OCH₂CONH₂ Cl 100 H CN₄H Cl 101 CO₂Et H OCH₃ 102CO₂H H OCH₃ 103 CH₂CO₂Et H OCH₃ 104 CH₂CO₂H H OCH₃ 105 OCH₂CO₂Et H OCH₃106 OCH₂CO₂H H OCH₃ 107 OCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 108 OCH₂CH₂CH₂PO(OH)₂H OCH₃ 109 OCH₂C₆H₄CO₂Et H OCH₃ 110 OCH₂C₆H₄CO₂H H OCH₃ 111 NHCH₂CO₂Et HOCH₃ 112 NHCH₂CO₂H H OCH₃ 113 NHCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 114NHCH₂CH₂CH₂PO(OH)₂ H OCH₃ 115 NHCH₂C₆H₄CO₂Et H OCH₃ 116 NHCH₂C₆H₄CO₂H HOCH₃ 117 NHCOCH₂CH₂CO₂Et H OCH₃ 118 NHCOCH₂CH₂CO₂H H OCH₃ 119 NHSO₂CH₃ HOCH₃ 120 NHCH₂CH═CHCO₂Et H OCH₃ 121 NHCH₂CH═CHCO₂H H OCH₃ 122 CONH₂ HOCH₃ 123 CH₂CONH₂ H OCH₃ 124 OCH₂CONH₂ H OCH₃ 125 CN₄H H OCH₃ 126 HCO₂Et OCH₃ 127 H CO₂H OCH₃ 128 H CH₂CO₂Et OCH₃ 129 H CH₂CO₂H OCH₃ 130 HOCH₂CO₂Et OCH₃ 131 H OCH₂CO₂H OCH₃ 132 H OCH₂CH₂CH₂PO(OEt)₂ OCH₃ 133 HOCH₂CH₂CH₂PO(OH)₂ OCH₃ 134 H OCH₂C₆H₄CO₂Et OCH₃ 135 H OCH₂C₆H₄CO₂H OCH₃136 H NHCH₂CO₂Et OCH₃ 137 H NHCH₂CO₂H OCH₃ 138 H NHCH₂CH₂CH₂PO(OEt)₂OCH₃ 139 H NHCH₂CH₂CH₂PO(OH)₂ OCH₃ 140 H NHCH₂C₆H₄CO₂Et OCH₃ 141 HNHCH₂C₆H₄CO₂H OCH₃ 142 H NHCOCH₂CH₂CO₂Et OCH₃ 143 H NHCOCH₂CH₂CO₂H OCH₃144 H NHSO₂CH₃ OCH₃ 145 H NHCH₂CH═CHCO₂Et OCH₃ 146 H NHCH₂CH═CHCO₂H OCH₃147 H CONH₂ OCH₃ 148 H CH₂CONH₂ OCH₃ 149 H OCH₂CONH₂ OCH₃ 150 H CN₄HOCH₃ 151 CO₂Et H CH₃ 152 CO₂H H CH₃ 153 CH₂CO₂Et H CH₃ 154 CH₂CO₂H H CH₃155 OCH₂CO₂Et H CH₃ 156 OCH₂CO₂H H CH₃ 157 OCH₂CH₂CH₂PO(OEt)₂ H CH₃ 158OCH₂CH₂CH₂PO(OH)₂ H CH₃ 159 OCH₂C₆H₄CO₂Et H CH₃ 160 OCH₂C₆H₄CO₂H H CH₃161 NHCH₂CO₂Et H CH₃ 162 NHCH₂CO₂H H CH₃ 163 NHCH₂CH₂CH₂PO(OEt)₂ H CH₃164 NHCH₂CH₂CH₂PO(OH)₂ H CH₃ 165 NHCH₂C₆H₄CO₂Et H CH₃ 166 NHCH₂C₆H₄CO₂HH CH₃ 167 NHCOCH₂CH₂CO₂Et H CH₃ 168 NHCOCH₂CH₂CO₂H H CH₃ 69 NHSO₂CH₃ HCH₃ 170 NHCH₂CH═CHCO₂Et H CH₃ 171 NHCH₂CH═CHCO₂H H CH₃ 172 CONH₂ H CH₃173 CH₂CONH₂ H CH₃ 174 OCH₂CONH₂ H CH₃ 175 CN₄H H CH₃ 176 H CO₂Et CH₃177 H CO₂H CH₃ 178 H CH₂CO₂Et CH₃ 179 H CH₂CO₂H CH₃ 180 H OCH₂CO₂Et CH₃181 H OCH₂CO₂H CH₃ 182 H OCH₂CH₂CH₂PO(OEt)₂ CH₃ 183 H OCH₂CH₂CH₂PO(OH)₂CH₃ 184 H OCH₂C₆H₄CO₂Et CH₃ 185 H OCH₂C₆H₄CO₂H CH₃ 186 H NHCH₂CO₂Et CH₃187 H NHCH₂CO₂H CH₃ 188 H NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 189 HNHCH₂CH₂CH₂PO(OH)₂ CH₃ 190 H NHCH₂C₆H₄CO₂Et CH₃ 191 H NHCH₂C₆H₄CO₂H CH₃192 H NHCOCH₂CH₂CO₂Et CH₃ 193 H NHCOCH₂CH₂CO₂H CH₃ 194 H NHSO₂CH₃ CH₃195 H NHCH₂CH═CHCO₂Et CH₃ 196 H NHCH₂CH═CHCO₂H CH₃ 197 H CONH₂ CH₃ 198 HCH₂CONH₂ CH₃ 199 H OCH₂CONH₂ CH₃ 200 H CN₄H CH₃ 201 CO₂Et Cl H 202 CO₂HCl H 203 CH₂CO₂Et Cl H 204 CH₂CO₂H Cl H 205 OCH₂CO₂Et Cl H 206 OCH₂CO₂HCl H 207 OCH₂CH₂CH₂PO(OEt)₂ Cl H 208 OCH₂CH₂CH₂PO(OH)₂ Cl H 209OCH₂C₆H₄CO₂Et Cl H 210 OCH₂C₆H₄CO₂H Cl H 211 NHCH₂CO₂Et Cl H 212NHCH₂CO₂H Cl H 213 NHCH₂CH₂CH₂PO(OEt)₂ Cl H 214 NHCH₂CH₂CH₂PO(OH)₂ Cl H215 NHCH₂C₆H₄CO₂Et Cl H 216 NHCH₂C₆H₄CO₂H Cl H 217 NHCOCH₂CH₂CO₂Et Cl H218 NHCOCH₂CH₂CO₂H Cl H 219 NHSO₂CH₃ Cl H 220 NHCH₂CH═CHCO₂Et Cl H 221NHCH₂CH═CHCO₂H Cl H 222 CONH₂ Cl H 223 CH₂CONH₂ Cl H 224 OCH₂CONH₂ Cl H225 CN₄H Cl H 226 Cl CO₂Et H 227 Cl CO₂H H 228 Cl CH₂CO₂Et H 229 ClCH₂CO₂H H 230 Cl OCH₂CO₂Et H 231 Cl OCH₂CO₂H H 232 Cl OCH₂CH₂CH₂PO(OEt)₂H 233 Cl OCH₂CH₂CH₂PO(OH)₂ H 234 Cl OCH₂C₆H₄CO₂Et H 235 Cl OCH₂C₆H₄CO₂HH 236 Cl NHCH₂CO₂Et H 237 Cl NHCH₂CO₂H H 238 Cl NHCH₂CH₂CH₂PO(OEt)₂ H239 Cl NHCH₂CH₂CH₂PO(OH)₂ H 240 Cl NHCH₂C₆H₄CO₂Et H 241 Cl NHCH₂C₆H₄CO₂HH 242 Cl NHCOCH₂CH₂CO₂Et H 243 Cl NHCOCH₂CH₂CO₂H H 244 Cl NHSO₂CH₃ H 245Cl NHCH₂CH═CHCO₂Et H 246 Cl NHCH₂CH═CHCO₂H H 247 Cl CONH₂ H 248 ClCH₂CONH₂ H 249 Cl OCH₂CONH₂ H 250 Cl CN₄H H 251 CO₂Et Cl Cl 252 CO₂H ClCl 253 CH₂CO₂Et Cl Cl 254 CH₂CO₂H Cl Cl 255 OCH₂CO₂Et Cl Cl 256 OCH₂CO₂HCl Cl 257 OCH₂CH₂CH₂PO(OEt)₂ Cl Cl 258 OCH₂CH₂CH₂PO(OH)₂ Cl Cl 259OCH₂C₆H₄CO₂Et Cl Cl 260 OCH₂C₆H₄CO₂H Cl Cl 261 NHCH₂CO₂Et Cl Cl 262NHCH₂CO₂H Cl Cl 263 NHCH₂CH₂CH₂PO(OEt)₂ Cl Cl 264 NHCH₂CH₂CH₂PO(OH)₂ ClCl 265 NHCH₂C₆H₄CO₂Et Cl Cl 266 NHCH₂C₆H₄CO₂H Cl Cl 267 NHCOCH₂CH₂CO₂EtCl Cl 268 NHCOCH₂CH₂CO₂H Cl Cl 269 NHSO₂CH₃ Cl Cl 270 NHCH₂CH═CHCO₂Et ClCl 271 NHCH₂CH═CHCO₂H Cl Cl 272 CONH₂ Cl Cl 273 CH₂CONH₂ Cl Cl 274OCH₂CONH₂ Cl Cl 275 CN₄H Cl Cl 276 Cl CO₂Et Cl 277 Cl CO₂H Cl 278 ClCH₂CO₂Et Cl 279 Cl CH₂CO₂H Cl 280 Cl OCH₂CO₂Et Cl 281 Cl OCH₂CO₂H Cl 282Cl OCH₂CH₂CH₂PO(OEt)₂ Cl 283 Cl OCH₂CH₂CH₂PO(OH)₂ Cl 284 ClOCH₂C₆H₄CO₂Et Cl 285 Cl OCH₂C₆H₄CO₂H Cl 286 Cl NHCH₂CO₂Et Cl 287 ClNHCH₂CO₂H Cl 288 Cl NHCH₂CH₂CH₂PO(OEt)₂ Cl 289 Cl NHCH₂CH₂CH₂PO(OH)₂ Cl290 Cl NHCH₂C₆H₄CO₂Et Cl 291 Cl NHCH₂C₆H₄CO₂H Cl 292 Cl NHCOCH₂CH₂CO₂EtCl 293 Cl NHCOCH₂CH₂CO₂H Cl 294 Cl NHSO₂CH₃ Cl 295 Cl NHCH₂CH═CHCO₂Et Cl296 Cl NHCH₂CH═CHCO₂H Cl 297 Cl CONH₂ Cl 298 Cl CH₂CONH₂ Cl 299 ClOCH₂CONH₂ Cl 300 Cl CN₄H Cl 301 CO₂Et Cl OCH₃ 302 CO₂H Cl OCH₃ 303CH₂CO₂Et Cl OCH₃ 304 CH₂CO₂H Cl OCH₃ 305 OCH₂CO₂Et Cl OCH₃ 306 OCH₂CO₂HCl OCH₃ 307 OCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 308 OCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 309OCH₂C₆H₄CO₂Et Cl OCH₃ 310 OCH₂C₆H₄CO₂H Cl OCH₃ 311 NHCH₂CO₂Et Cl OCH₃312 NHCH₂CO₂H Cl OCH₃ 313 NHCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 314NHCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 315 NHCH₂C₆H₄CO₂Et Cl OCH₃ 316 NHCH₂C₆H₄CO₂HCl OCH₃ 317 NHCOCH₂CH₂CO₂Et Cl OCH₃ 318 NHCOCH₂CH₂CO₂H Cl OCH₃ 319NHSO₂CH₃ Cl OCH₃ 320 NHCH₂CH═CHCO₂Et Cl OCH₃ 321 NHCH₂CH═CHCO₂H Cl OCH₃322 CONH₂ Cl OCH₃ 323 CH₂CONH₂ Cl OCH₃ 324 OCH₂CONH₂ Cl OCH₃ 325 CN₄H ClOCH₃ 326 Cl CO₂Et OCH₃ 327 Cl CO₂H OCH₃ 328 Cl CH₂CO₂Et OCH₃ 329 ClCH₂CO₂H OCH₃ 330 Cl OCH₂CO₂Et OCH₃ 331 Cl OCH₂CO₂H OCH₃ 332 ClOCH₂CH₂CH₂PO(OEt)₂ OCH₃ 333 Cl OCH₂CH₂CH₂PO(OH)₂ OCH₃ 334 ClOCH₂C₆H₄CO₂Et OCH₃ 335 Cl OCH₂C₆H₄CO₂H OCH₃ 336 Cl NHCH₂CO₂Et OCH₃ 337Cl NHCH₂CO₂H OCH₃ 338 Cl NHCH₂CH₂CH₂PO(OEt)₂ OCH₃ 339 ClNHCH₂CH₂CH₂PO(OH)₂ OCH₃ 340 Cl NHCH₂C₆H₄CO₂Et OCH₃ 341 Cl NHCH₂C₆H₄CO₂HOCH₃ 342 Cl NHCOCH₂CH₂CO₂Et OCH₃ 343 Cl NHCOCH₂CH₂CO₂H OCH₃ 344 ClNHSO₂CH₃ OCH₃ 345 Cl NHCH₂CH═CHCO₂Et OCH₃ 346 Cl NHCH₂CH═CHCO₂H OCH₃ 347Cl CONH₂ OCH₃ 348 Cl CH₂CONH₂ OCH₃ 349 Cl OCH₂CONH₂ OCH₃ 350 Cl CN₄HOCH₃ 351 CO₂Et Cl CH₃ 352 CO₂H Cl CH₃ 353 CH₂CO₂Et Cl CH₃ 354 CH₂CO₂H ClCH₃ 355 OCH₂CO₂Et Cl CH₃ 356 OCH₂CO₂H Cl CH₃ 357 OCH₂CH₂CH₂PO(OEt)₂ ClCH₃ 358 OCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 359 OCH₂C₆H₄CO₂Et Cl CH₃ 360OCH₂C₆H₄CO₂H Cl CH₃ 361 NHCH₂CO₂Et Cl CH₃ 362 NHCH₂CO₂H Cl CH₃ 363NHCH₂CH₂CH₂PO(OEt)₂ Cl CH₃ 364 NHCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 365NHCH₂C₆H₄CO₂Et Cl CH₃ 366 NHCH₂C₆H₄CO₂H Cl CH₃ 367 NHCOCH₂CH₂CO₂Et ClCH₃ 368 NHCOCH₂CH₂CO₂H Cl CH₃ 369 NHSO₂CH₃ Cl CH₃ 370 NHCH₂CH═CHCO₂Et ClCH₃ 371 NHCH₂CH═CHCO₂H Cl CH₃ 372 CONH₂ Cl CH₃ 373 CH₂CONH₂ Cl CH₃ 374OCH₂CONH₂ Cl CH₃ 375 CN₄H Cl CH₃ 376 Cl CO₂Et CH₃ 377 Cl CO₂H CH₃ 378 ClCH₂CO₂Et CH₃ 379 Cl CH₂CO₂H CH₃ 380 Cl OCH₂CO₂Et CH₃ 381 Cl OCH₂CO₂H CH₃382 Cl OCH₂CH₂CH₂PO(OEt)₂ CH₃ 383 Cl OCH₂CH₂CH₂PO(OH)₂ CH₃ 384 ClOCH₂C₆H₄CO₂Et CH₃ 385 Cl OCH₂C₆H₄CO₂H CH₃ 386 Cl NHCH₂CO₂Et CH₃ 387 ClNHCH₂CO₂H CH₃ 388 Cl NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 389 Cl NHCH₂CH₂CH₂PO(OH)₂CH₃ 390 Cl NHCH₂C₆H₄CO₂Et CH₃ 391 Cl NHCH₂C₆H₄CO₂H CH₃ 392 ClNHCOCH₂CH₂CO₂Et CH₃ 393 Cl NHCOCH₂CH₂CO₂H CH₃ 394 Cl NHSO₂CH₃ CH₃ 395 ClNHCH₂CH═CHCO₂Et CH₃ 396 Cl NHCH₂CH═CHCO₂H CH₃ 397 Cl CONH₂ CH₃ 398 ClCH₂CONH₂ CH₃ 399 Cl OCH₂CONH₂ CH₃ 400 Cl CN₄H CH₃

TABLE 2b

Ex. # X Y X′ 1 CO₂Et H H 2 CO₂H H H 3 CH₂CO₂Et H H 4 CH₂CO₂H H H 5OCH₂CO₂Et H H 6 OCH₂CO₂H H H 7 OCH₂CH₂CH₂PO(OEt)₂ H H 8OCH₂CH₂CH₂PO(OH)₂ H H 9 OCH₂C₆H₄CO₂Et H H 10 OCH₂C₆H₄CO₂H H H 11NHCH₂CO₂Et H H 12 NHCH₂CO₂H H H 13 NHCH₂CH₂CH₂PO(OEt)₂ H H 14NHCH₂CH₂CH₂PO(OH)₂ H H 15 NHCH₂C₆H₄CO₂Et H H 16 NHCH₂C₆H₄CO₂H H H 17NHCOCH₂CH₂CO₂Et H H 18 NHCOCH₂CH₂CO₂H H H 19 NHSO₂CH₃ H H 20NHCH₂CH═CHCO₂Et H H 21 NHCH₂CH═CHCO₂H H H 22 CONH₂ H H 23 CH₂CONH₂ H H24 OCH₂CONH₂ H H 25 CN₄H H H 26 H CO₂Et H 27 H CO₂H H 28 H CH₂CO₂Et H 29H CH₂CO₂H H 30 H OCH₂CO₂Et H 31 H OCH₂CO₂H H 32 H OCH₂CH₂CH₂PO(OEt)₂ H33 H OCH₂CH₂CH₂PO(OH)₂ H 34 H OCH₂C₆H₄CO₂Et H 35 H OCH₂C₆H₄CO₂H H 36 HNHCH₂CO₂Et H 37 H NHCH₂CO₂H H 38 H NHCH₂CH₂CH₂PO(OEt)₂ H 39 HNHCH₂CH₂CH₂PO(OH)₂ H 40 H NHCH₂C₆H₄CO₂Et H 41 H NHCH₂C₆H₄CO₂H H 42 HNHCOCH₂CH₂CO₂Et H 43 H NHCOCH₂CH₂CO₂H H 44 H NHSO₂CH₃ H 45 HNHCH₂CH═CHCO₂Et H 46 H NHCH₂CH═CHCO₂H H 47 H CONH₂ H 48 H CHCONH₂ H 49 HOCH₂CONH₂ H 50 H CN₄H H 51 CO₂Et H Cl 52 CO₂H H Cl 53 CH₂CO₂Et H Cl 54CH₂CO₂H H Cl 55 OCH₂CO₂Et H Cl 56 OCH₂CO₂H H Cl 57 OCH₂CH₂CH₂PO(OEt)₂ HCl 58 OCH₂CH₂CH₂PO(OH)₂ H Cl 59 OCH₂C₆H₄CO₂Et H Cl 60 OCH₂C₆H₄CO₂H H Cl61 NHCH₂CO₂Et H Cl 62 NHCH₂CO₂H H Cl 63 NHCH₂CH₂CH₂PO(OEt)₂ H Cl 64NHCH₂CH₂CH₂PO(OH)₂ H Cl 65 NHCH₂C₆H₄CO₂Et H Cl 66 NHCH₂C₆H₄CO₂H H Cl 67NHCOCH₂CH₂CO₂Et H Cl 68 NHCOCH₂CH₂CO₂H H Cl 69 NHSO₂CH₃ H Cl 70NHCH₂CH═CHCO₂Et H Cl 71 NHCH₂CH═CHCO₂H H Cl 72 CONH₂ H Cl 73 CH₂CONH₂ HCl 74 OCH₂CONH₂ H Cl 75 CN₄H H Cl 76 H CO₂Et Cl 77 H CO₂H Cl 78 HCH₂CO₂Et Cl 79 H CH₂CO₂H Cl 80 H OCH₂CO₂Et Cl 81 H OCH₂CO₂H Cl 82 HOCH₂CH₂CH₂PO(OEt)₂ Cl 83 H OCH₂CH₂CH₂PO(OH)₂ Cl 84 H OCH₂C₆H₄CO₂Et Cl 85H OCH₂C₆H₄CO₂H Cl 86 H NHCH₂CO₂Et Cl 87 H NHCH₂CO₂H Cl 88 HNHCH₂CH₂CH₂PO(OEt)₂ Cl 89 H NHCH₂CH₂CH₂PO(OH)₂ Cl 90 H NHCH₂C₆H₄CO₂Et Cl91 H NHCH₂C₆H₄CO₂H Cl 92 H NHCOCH₂CH₂CO₂Et Cl 93 H NHCOCH₂CH₂CO₂H Cl 94H NHSO₂CH₃ Cl 95 H NHCH₂CH═CHCO₂Et Cl 96 H NHCH₂CH═CHCO₂H Cl 97 H CONH₂Cl 98 H CH₂CONH₂ Cl 99 H OCH₂CONH₂ Cl 100 H CN₄H Cl 101 CO₂Et H OCH₃ 102CO₂H H OCH₃ 103 CH₂CO₂Et H OCH₃ 104 CH₂CO₂H H OCH₃ 105 OCH₂CO₂Et H OCH₃106 OCH₂CO₂H H OCH₃ 107 OCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 108 OCH₂CH₂CH₂PO(OH)₂H OCH₃ 109 OCH₂C₆H₄CO₂Et H OCH₃ 110 OCH₂C₆H₄CO₂H H OCH₃ 111 NHCH₂CO₂Et HOCH₃ 112 NHCH₂CO₂H H OCH₃ 113 NHCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 114NHCH₂CH₂CH₂PO(OH)₂ H OCH₃ 115 NHCH₂C₆H₄CO₂Et H OCH₃ 116 NHCH₂C₆H₄CO₂H HOCH₃ 117 NHCOCH₂CH₂CO₂Et H OCH₃ 118 NHCOCH₂CH₂CO₂H H OCH₃ 119 NHSO₂CH₃ HOCH₃ 120 NHCH₂CH═CHCO₂Et H OCH₃ 121 NHCH₂CH═CHCO₂H H OCH₃ 122 CONH₂ HOCH₃ 123 CH₂CONH₂ H OCH₃ 124 OCH₂CONH₂ H OCH₃ 125 CN₄H H OCH₃ 126 HCO₂Et OCH₃ 127 H CO₂H OCH₃ 128 H CH₂CO₂Et OCH₃ 129 H CH₂CO₂H OCH₃ 130 HOCH₂CO₂Et OCH₃ 131 H OCH₂CO₂H OCH₃ 132 H OCH₂CH₂CH₂PO(OEt)₂ OCH₃ 133 HOCH₂CH₂CH₂PO(OH)₂ OCH₃ 134 H OCH₂C₆H₄CO₂Et OCH₃ 135 H OCH₂C₆H₄CO₂H OCH₃136 H NHCH₂CO₂Et OCH₃ 137 H NHCH₂CO₂H OCH₃ 138 H NHCH₂CH₂CH₂PO(OEt)₂OCH₃ 139 H NHCH₂CH₂CH₂PO(OH)₂ OCH₃ 140 H NHCH₂C₆H₄CO₂Et OCH₃ 141 HNHCH₂C₆H₄CO₂H OCH₃ 142 H NHCOCH₂CH₂CO₂Et OCH₃ 143 H NHCOCH₂CH₂CO₂H OCH₃144 H NHSO₂CH₃ OCH₃ 145 H NHCH₂CH═CHCO₂Et OCH₃ 146 H NHCH₂CH═CHCO₂H OCH₃147 H CONH₂ OCH₃ 148 H CH₂CONH₂ OCH₃ 149 H OCH₂CONH₂ OCH₃ 150 H CN₄HOCH₃ 151 CO₂Et H CH₃ 152 CO₂H H CH₃ 153 CH₂CO₂Et H CH₃ 154 CH₂CO₂H H CH₃155 OCH₂CO₂Et H CH₃ 156 OCH₂CO₂H H CH₃ 157 OCH₂CH₂CH₂PO(OEt)₂ H CH₃ 158OCH₂CH₂CH₂PO(OH)₂ H CH₃ 159 OCH₂C₆H₄CO₂Et H CH₃ 160 OCH₂C₆H₄CO₂H H CH₃161 NHCH₂CO₂Et H CH₃ 162 NHCH₂CO₂H H CH₃ 163 NHCH₂CH₂CH₂PO(OEt)₂ H CH₃164 NHCH₂CH₂CH₂PO(OH)₂ H CH₃ 165 NHCH₂C₆H₄CO₂Et H CH₃ 166 NHCH₂C₆H₄CO₂HH CH₃ 167 NHCOCH₂CH₂CO₂Et H CH₃ 168 NHCOCH₂CH₂CO₂H H CH₃ 69 NHSO₂CH₃ HCH₃ 170 NHCH₂CH═CHCO₂Et H CH₃ 171 NHCH₂CH═CHCO₂H H CH₃ 172 CONH₂ H CH₃173 CH₂CONH₂ H CH₃ 174 OCH₂CONH₂ H CH₃ 175 CN₄H H CH₃ 176 H CO₂Et CH₃177 H CO₂H CH₃ 178 H CH₂CO₂Et CH₃ 179 H CH₂CO₂H CH₃ 180 H OCH₂CO₂Et CH₃181 H OCH₂CO₂H CH₃ 182 H OCH₂CH₂CH₂PO(OEt)₂ CH₃ 183 H OCH₂CH₂CH₂PO(OH)₂CH₃ 184 H OCH₂C₆H₄CO₂Et CH₃ 185 H OCH₂C₆H₄CO₂H CH₃ 186 H NHCH₂CO₂Et CH₃187 H NHCH₂CO₂H CH₃ 188 H NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 189 HNHCH₂CH₂CH₂PO(OH)₂ CH₃ 190 H NHCH₂C₆H₄CO₂Et CH₃ 191 H NHCH₂C₆H₄CO₂H CH₃192 H NHCOCH₂CH₂CO₂Et CH₃ 193 H NHCOCH₂CH₂CO₂H CH₃ 194 H NHSO₂CH₃ CH₃195 H NHCH₂CH═CHCO₂Et CH₃ 196 H NHCH₂CH═CHCO₂H CH₃ 197 H CONH₂ CH₃ 198 HCH₂CONH₂ CH₃ 199 H OCH₂CONH₂ CH₃ 200 H CN₄H CH₃ 201 CO₂Et Cl H 202 CO₂HCl H 203 CH₂CO₂Et Cl H 204 CH₂CO₂H Cl H 205 OCH₂CO₂Et Cl H 206 OCH₂CO₂HCl H 207 OCH₂CH₂CH₂PO(OEt)₂ Cl H 208 OCH₂CH₂CH₂PO(OH)₂ Cl H 209OCH₂C₆H₄CO₂Et Cl H 210 OCH₂C₆H₄CO₂H Cl H 211 NHCH₂CO₂Et Cl H 212NHCH₂CO₂H Cl H 213 NHCH₂CH₂CH₂PO(OEt)₂ Cl H 214 NHCH₂CH₂CH₂PO(OH)₂ Cl H215 NHCH₂C₆H₄CO₂Et Cl H 216 NHCH₂C₆H₄CO₂H Cl H 217 NHCOCH₂CH₂CO₂Et Cl H218 NHCOCH₂CH₂CO₂H Cl H 219 NHSO₂CH₃ Cl H 220 NHCH₂CH═CHCO₂Et Cl H 221NHCH₂CH═CHCO₂H Cl H 222 CONH₂ Cl H 223 CH₂CONH₂ Cl H 224 OCH₂CONH₂ Cl H225 CN₄H Cl H 226 Cl CO₂Et H 227 Cl CO₂H H 228 Cl CH₂CO₂Et H 229 ClCH₂CO₂H H 230 Cl OCH₂CO₂Et H 231 Cl OCH₂CO₂H H 232 Cl OCH₂CH₂CH₂PO(OEt)₂H 233 Cl OCH₂CH₂CH₂PO(OH)₂ H 234 Cl OCH₂C₆H₄CO₂Et H 235 Cl OCH₂C₆H₄CO₂HH 236 Cl NHCH₂CO₂Et H 237 Cl NHCH₂CO₂H H 238 Cl NHCH₂CH₂CH₂PO(OEt)₂ H239 Cl NHCH₂CH₂CH₂PO(OH)₂ H 240 Cl NHCH₂C₆H₄CO₂Et H 241 Cl NHCH₂C₆H₄CO₂HH 242 Cl NHCOCH₂CH₂CO₂Et H 243 Cl NHCOCH₂CH₂CO₂H H 244 Cl NHSO₂CH₃ H 245Cl NHCH₂CH═CHCO₂Et H 246 Cl NHCH₂CH═CHCO₂H H 247 Cl CONH₂ H 248 ClCH₂CONH₂ H 249 Cl OCH₂CONH₂ H 250 Cl CN₄H H 251 CO₂Et Cl Cl 252 CO₂H ClCl 253 CH₂CO₂Et Cl Cl 254 CH₂CO₂H Cl Cl 255 OCH₂CO₂Et Cl Cl 256 OCH₂CO₂HCl Cl 257 OCH₂CH₂CH₂PO(OEt)₂ Cl Cl 258 OCH₂CH₂CH₂PO(OH)₂ Cl Cl 259OCH₂C₆H₄CO₂Et Cl Cl 260 OCH₂C₆H₄CO₂H Cl Cl 261 NHCH₂CO₂Et Cl Cl 262NHCH₂CO₂H Cl Cl 263 NHCH₂CH₂CH₂PO(OEt)₂ Cl Cl 264 NHCH₂CH₂CH₂PO(OH)₂ ClCl 265 NHCH₂C₆H₄CO₂Et Cl Cl 266 NHCH₂C₆H₄CO₂H Cl Cl 267 NHCOCH₂CH₂CO₂EtCl Cl 268 NHCOCH₂CH₂CO₂H Cl Cl 269 NHSO₂CH₃ Cl Cl 270 NHCH₂CH═CHCO₂Et ClCl 271 NHCH₂CH═CHCO₂H Cl Cl 272 CONH₂ Cl Cl 273 CH₂CONH₂ Cl Cl 274OCH₂CONH₂ Cl Cl 275 CN₄H Cl Cl 276 Cl CO₂Et Cl 277 Cl CO₂H Cl 278 ClCH₂CO₂Et Cl 279 Cl CH₂CO₂H Cl 280 Cl OCH₂CO₂Et Cl 281 Cl OCH₂CO₂H Cl 282Cl OCH₂CH₂CH₂PO(OEt)₂ Cl 283 Cl OCH₂CH₂CH₂PO(OH)₂ Cl 284 ClOCH₂C₆H₄CO₂Et Cl 285 Cl OCH₂C₆H₄CO₂H Cl 286 Cl NHCH₂CO₂Et Cl 287 ClNHCH₂CO₂H Cl 288 Cl NHCH₂CH₂CH₂PO(OEt)₂ Cl 289 Cl NHCH₂CH₂CH₂PO(OH)₂ Cl290 Cl NHCH₂C₆H₄CO₂Et Cl 291 Cl NHCH₂C₆H₄CO₂H Cl 292 Cl NHCOCH₂CH₂CO₂EtCl 293 Cl NHCOCH₂CH₂CO₂H Cl 294 Cl NHSO₂CH₃ Cl 295 Cl NHCH₂CH═CHCO₂Et Cl296 Cl NHCH₂CH═CHCO₂H Cl 297 Cl CONH₂ Cl 298 Cl CH₂CONH₂ Cl 299 ClOCH₂CONH₂ Cl 300 Cl CN₄H Cl 301 CO₂Et Cl OCH₃ 302 CO₂H Cl OCH₃ 303CH₂CO₂Et Cl OCH₃ 304 CH₂CO₂H Cl OCH₃ 305 OCH₂CO₂Et Cl OCH₃ 306 OCH₂CO₂HCl OCH₃ 307 OCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 308 OCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 309OCH₂C₆H₄CO₂Et Cl OCH₃ 310 OCH₂C₆H₄CO₂H Cl OCH₃ 311 NHCH₂CO₂Et Cl OCH₃312 NHCH₂CO₂H Cl OCH₃ 313 NHCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 314NHCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 315 NHCH₂C₆H₄CO₂Et Cl OCH₃ 316 NHCH₂C₆H₄CO₂HCl OCH₃ 317 NHCOCH₂CH₂CO₂Et Cl OCH₃ 318 NHCOCH₂CH₂CO₂H Cl OCH₃ 319NHSO₂CH₃ Cl OCH₃ 320 NHCH₂CH═CHCO₂Et Cl OCH₃ 321 NHCH₂CH═CHCO₂H Cl OCH₃322 CONH₂ Cl OCH₃ 323 CH₂CONH₂ Cl OCH₃ 324 OCH₂CONH₂ Cl OCH₃ 325 CN₄H ClOCH₃ 326 Cl CO₂Et OCH₃ 327 Cl CO₂H OCH₃ 328 Cl CH₂CO₂Et OCH₃ 329 ClCH₂CO₂H OCH₃ 330 Cl OCH₂CO₂Et OCH₃ 331 Cl OCH₂CO₂H OCH₃ 332 ClOCH₂CH₂CH₂PO(OEt)₂ OCH₃ 333 Cl OCH₂CH₂CH₂PO(OH)₂ OCH₃ 334 ClOCH₂C₆H₄CO₂Et OCH₃ 335 Cl OCH₂C₆H₄CO₂H OCH₃ 336 Cl NHCH₂CO₂Et OCH₃ 337Cl NHCH₂CO₂H OCH₃ 338 Cl NHCH₂CH₂CH₂PO(OEt)₂ OCH₃ 339 ClNHCH₂CH₂CH₂PO(OH)₂ OCH₃ 340 Cl NHCH₂C₆H₄CO₂Et OCH₃ 341 Cl NHCH₂C₆H₄CO₂HOCH₃ 342 Cl NHCOCH₂CH₂CO₂Et OCH₃ 343 Cl NHCOCH₂CH₂CO₂H OCH₃ 344 ClNHSO₂CH₃ OCH₃ 345 Cl NHCH₂CH═CHCO₂Et OCH₃ 346 Cl NHCH₂CH═CHCO₂H OCH₃ 347Cl CONH₂ OCH₃ 348 Cl CH₂CONH₂ OCH₃ 349 Cl OCH₂CONH₂ OCH₃ 350 Cl CN₄HOCH₃ 351 CO₂Et Cl CH₃ 352 CO₂H Cl CH₃ 353 CH₂CO₂Et Cl CH₃ 354 CH₂CO₂H ClCH₃ 355 OCH₂CO₂Et Cl CH₃ 356 OCH₂CO₂H Cl CH₃ 357 OCH₂CH₂CH₂PO(OEt)₂ ClCH₃ 358 OCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 359 OCH₂C₆H₄CO₂Et Cl CH₃ 360OCH₂C₆H₄CO₂H Cl CH₃ 361 NHCH₂CO₂Et Cl CH₃ 362 NHCH₂CO₂H Cl CH₃ 363NHCH₂CH₂CH₂PO(OEt)₂ Cl CH₃ 364 NHCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 365NHCH₂C₆H₄CO₂Et Cl CH₃ 366 NHCH₂C₆H₄CO₂H Cl CH₃ 367 NHCOCH₂CH₂CO₂Et ClCH₃ 368 NHCOCH₂CH₂CO₂H Cl CH₃ 369 NHSO₂CH₃ Cl CH₃ 370 NHCH₂CH═CHCO₂Et ClCH₃ 371 NHCH₂CH═CHCO₂H Cl CH₃ 372 CONH₂ Cl CH₃ 373 CH₂CONH₂ Cl CH₃ 374OCH₂CONH₂ Cl CH₃ 375 CN₄H Cl CH₃ 376 Cl CO₂Et CH₃ 377 Cl CO₂H CH₃ 378 ClCH₂CO₂Et CH₃ 379 Cl CH₂CO₂H CH₃ 380 Cl OCH₂CO₂Et CH₃ 381 Cl OCH₂CO₂H CH₃382 Cl OCH₂CH₂CH₂PO(OEt)₂ CH₃ 383 Cl OCH₂CH₂CH₂PO(OH)₂ CH₃ 384 ClOCH₂C₆H₄CO₂Et CH₃ 385 Cl OCH₂C₆H₄CO₂H CH₃ 386 Cl NHCH₂CO₂Et CH₃ 387 ClNHCH₂CO₂H CH₃ 388 Cl NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 389 Cl NHCH₂CH₂CH₂PO(OH)₂CH₃ 390 Cl NHCH₂C₆H₄CO₂Et CH₃ 391 Cl NHCH₂C₆H₄CO₂H CH₃ 392 ClNHCOCH₂CH₂CO₂Et CH₃ 393 Cl NHCOCH₂CH₂CO₂H CH₃ 394 Cl NHSO₂CH₃ CH₃ 395 ClNHCH₂CH═CHCO₂Et CH₃ 396 Cl NHCH₂CH═CHCO₂H CH₃ 397 Cl CONH₂ CH₃ 398 ClCH₂CONH₂ CH₃ 399 Cl OCH₂CONH₂ CH₃ 400 Cl CN₄H CH₃

TABLE 3a

Ex. # X′ Y′ X 1 CO₂Et H H 2 CO₂H H H 3 CH₂CO₂Et H H 4 CH₂CO₂H H H 5OCH₂CO₂Et H H 6 OCH₂CO₂H H H 7 OCH₂CH₂CH₂PO(OEt)₂ H H 8OCH₂CH₂CH₂PO(OH)₂ H H 9 OCH₂C₆H₄CO₂Et H H 10 OCH₂C₆H₄CO₂H H H 11NHCH₂CO₂Et H H 12 NHCH₂CO₂H H H 13 NHCH₂ CH₂CH₂PO(OEt)₂ H H 14NHCH₂CH₂CH₂PO(OH)₂ H H 15 NHCH₂C₆H₄CO₂Et H H 16 NHCH₂C₆H₄CO₂H H H 17NHCOCH₂CH₂CO₂Et H H 18 NHCOCH₂CH₂CO₂H H H 19 NHSO₂CH₃ H H 20NHCH₂CH═CHCO₂Et H H 21 NHCH₂CH═CHCO₂H H H 22 CONH₂ H H 23 CH₂CONH₂ H H24 OCH₂CONH₂ H H 25 CN₄H H H 26 H CO₂Et H 27 H CO₂H H 28 H CH₂CO₂Et H 29H CH₂CO₂H H 30 H OCH₂CO₂Et H 31 H OCH₂CO₂H H 32 H OCH₂CH₂CH₂PO(OEt)₂ H33 H OCH₂CH₂CH₂PO(OH)₂ H 34 H OCH₂C₆H₄CO₂Et H 35 H OCH₂C₆H₄CO₂H H 36 HNHCH₂CO₂Et H 37 H NHCH₂CO₂H H 38 H NHCH₂CH₂CH₂PO(OEt)₂ H 39 HNHCH₂CH₂CH₂PO(OH)₂ H 40 H NHCH₂C₆H₄CO₂Et H 41 H NHCH₂C₆H₄CO₂H H 42 HNHCOCH₂CH₂CO₂Et H 43 H NHCOCH₂CH₂CO₂H H 44 H NHSO₂CH₃ H 45 HNHCH₂CH═CHCO₂Et H 46 H NHCH₂CH═CHCO₂H H 47 H CONH₂ H 48 H CH₂CONH₂ H 49H OCH₂CONH₂ H 50 H CN₄H H 51 CO₂Et H Cl 52 CO₂H H Cl 53 CH₂CO₂Et H Cl 54CH₂CO₂H H Cl 55 OCH₂CO₂Et H Cl 56 OCH₂CO₂H H Cl 57 OCH₂CH₂CH₂PO(OEt)₂ HCl 58 OCH₂CH₂CH₂PO(OH)₂ H Cl 59 OCH₂C₆H₄CO₂Et H Cl 60 OCH₂C₆H₄CO₂H H Cl61 NHCH₂CO₂Et H Cl 62 NHCH₂CO₂H H Cl 63 NHCH₂CH₂CH₂PO(OEt)₂ H Cl 64NHCH₂CH₂CH₂PO(OH)₂ H Cl 65 NHCH₂C₆H₄CO₂Et H Cl 66 NHCH₂C₆H₄CO₂H H Cl 67NHCOCH₂CH₂CO₂Et H Cl 68 NHCOCH₂CH₂CO₂H H Cl 69 NHSO₂CH₃ H Cl 70NHCH₂CH═CHCO₂Et H Cl 71 NHCH₂CH═CHCO₂H H Cl 72 CONH₂ H Cl 73 CH₂CONH₂ HCl 74 OCH₂CONH₂ H Cl 75 CN₂H H Cl 76 H CO₂Et Cl 77 H CO₂H Cl 78 HCH₂CO₂Et Cl 79 H CH₂CO₂H Cl 80 H OCH₂CO₂Et Cl 81 H OCH₂CO₂H Cl 82 HOCH₂CH₂CH₂PO(OEt)₂ Cl 83 H OCH₂CH₂CH₂PO(OH)₂ Cl 84 H OCH₂C₆H₄CO₂Et Cl 85H OCH₂C₆H₄CO₂H Cl 86 H NHCH₂CO₂Et Cl 87 H NHCH₂CO₂H Cl 88 HNHCH₂CH₂CH₂PO(OEt)₂ Cl 89 H NHCH₂CH₂CH₂PO(OH)₂ Cl 90 H NHCH₂C₆H₄CO₂Et Cl91 H NHCH₂C₆H₄CO₂H Cl 92 H NHCOCH₂CH₂CO₂Et Cl 93 H NHCOCH₂CH₂CO₂H Cl 94H NHSO₂CH₃ Cl 95 H NHCH₂CH═CHCO₂Et Cl 96 H NHCH₂CH═CHCO₂H Cl 97 H CONH₂Cl 98 H CH₂CONH₂ Cl 99 H OCH₂CONH₂ Cl 100 H CN₂H Cl 101 CO₂Et H OCH₃ 102CO₂H H OCH₃ 103 CH₂CO₂Et H OCH₃ 104 CH₂CO₂H H OCH₃ 105 OCH₂CO₂Et H OCH₃106 OCH₂CO₂H H OCH₃ 107 OCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 108 OCH₂CH₂CH₂PO(OH)₂H OCH₃ 109 OCH₂C₆H₄CO₂Et H OCH₃ 110 OCH₂C₆H₄CO₂H H OCH₃ 111 NHCH₂CO₂Et HOCH₃ 112 NHCH₂CO₂H H OCH₃ 113 NHCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 114NHCH₂CH₂CH₂PO(OH)₂ H OCH₃ 115 NHCH₂C₆H₄CO₂Et H OCH₃ 116 NHCH₂C₆H₄CO₂H HOCH₃ 117 NHCOCH₂CH₂CO₂Et H OCH₃ 118 NHCOCH₂CH₂CO₂H H OCH₃ 119 NHSO₂CH₃ HOCH₃ 120 NHCH₂CH═CHCO₂Et H OCH₃ 121 NHCH₂CH═CHCO₂H H OCH₃ 122 CONH₂ HOCH₃ 123 CH₂CONH₂ H OCH₃ 124 OCH₂CONH₂ H OCH₃ 125 CN₄H H OCH₃ 126 HCO₂Et OCH₃ 127 H CO₂H OCH₃ 128 H CH₂CO₂Et OCH₃ 129 H CH₂CO₂H OCH₃ 130 HOCH₂CO₂Et OCH₃ 131 H OCH₂CO₂H OCH₃ 132 H OCH₂CH₂CH₂PO(OEt)₂ OCH₃ 133 HOCH₂CH₂CH₂PO(OH)₂ OCH₃ 134 H OCH₂C₆H₄CO₂Et OCH₃ 135 H OCH₂C₆H₄CO₂H OCH₃136 H NHCH₂CO₂Et OCH₃ 137 H NHCH₂CO₂H OCH₃ 138 H NHCH₂CH₂CH₂PO(OEt)₂OCH₃ 139 H NHCH₂CH₂CH₂PO(OH)₂ OCH₃ 140 H NHCH₂C₆H₄CO₂Et OCH₃ 141 HNHCH₂C₆H₄CO₂H OCH₃ 142 H NHCOCH₂CH₂CO₂Et OCH₃ 143 H NHCOCH₂CH₂CO₂H OCH₃144 H NHSO₂CH₃ OCH₃ 145 H NHCH₂CH═CHCO₂Et OCH₃ 146 H NHCH₂CH═CHCO₂H OCH₃147 H CONH₂ OCH₃ 148 H CH₂CONH₂ OCH₃ 149 H OCH₂CONH₂ OCH₃ 150 H CN₄HOCH₃ 151 CO₂Et H CH₃ 152 CO₂H H CH₃ 153 CH₂CO₂Et H CH₃ 154 CH₂CO₂H H CH₃155 OCH₂CO₂Et H CH₃ 156 OCH₂CO₂H H CH₃ 157 OCH₂CH₂CH₂PO(OEt)₂ H CH₃ 158OCH₂CH₂CH₂PO(OH)₂ H CH₃ 159 OCH₂C₆H₄CO₂Et H CH₃ 160 OCH₂C₆H₄CO₂H H CH₃161 NHCH₂CO₂Et H CH₃ 162 NHCH₂CO₂H H CH₃ 163 NHCH₂CH₂CH₂PO(OEt)₂ H CH₃164 NHCH₂CH₂CHPO(OH)₂ H CH₃ 165 NHCH₂C₆H₄CO₂Et H CH₃ 166 NHCH₂C₆H₄CO₂H HCH₃ 167 NHCOCH₂CH₂CO₂Et H CH₃ 168 NHCOCH₂CH₂CO₂H H CH₃ 169 NHSO₂CH₃ HCH₃ 170 NHCH₂CH═CHCO₂Et H CH₃ 171 NHCH₂CH═CHCO₂H H CH₃ 172 CONH₂ H CH₃173 CH₂CONH₂ H CH₃ 174 OCH₂CONH₂ H CH₃ 175 CN₄H H CH₃ 176 H CO₂Et CH₃177 H CO₂H CH₃ 178 H CH₂CO₂Et CH₃ 179 H CH₂CO₂H CH₃ 180 H OCH₂CO₂Et CH₃181 H OCH₂CO₂H CH₃ 182 H OCH₂CH₂CH₂PO(OEt)₂ CH₃ 183 H OCH₂CH₂CH₂PO(OH)₂CH₃ 184 H OCH₂C₆H₄CO₂Et CH₃ 185 H OCH₂C₆H₄CO₂H CH₃ 186 H NHCH₂CO₂Et CH₃187 H NHCH₂CO₂H CH₃ 188 H NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 189 HNHCH₂CH₂CH₂PO(OH)₂ CH₃ 190 H NHCH₂C₆H₄CO₂Et CH₃ 191 H NHCH₂C₆H₄CO₂H CH₃192 H NHCOCH₂CH₂CO₂Et CH₃ 193 H NHCOCH₂CH₂CO₂H CH₃ 194 H NHSO₂CH₃ CH₃195 H NHCH₂CH═CHCO₂Et CH₃ 196 H NHCH₂CH═CHCO₂H CH₃ 197 H CONH₂ CH₃ 198 HCH₂CONH₂ CH₃ 199 H OCH₂CONH₂ CH₃ 200 H CN₄H CH₃ 201 CO₂Et Cl H 202 CO₂HCl H 203 CH₂CO₂Et Cl H 204 CH₂CO₂H Cl H 205 OCH₂CO₂Et Cl H 206 OCH₂CO₂HCl H 207 OCH₂CH₂CH₂PO(OEt)₂ Cl H 208 OCH₂CH₂CH₂PO(OH)₂ Cl H 209OCH₂C₆H₄CO₂Et Cl H 210 OCH₂C₆H₄CO₂H Cl H 211 NHCH₂CO₂Et Cl H 212NHCH₂CO₂H Cl H 213 NHCH₂CH₂CH₂PO(OEt)₂ Cl H 214 NHCH₂CH₂CH₂PO(OH)₂ Cl H215 NHCH₂C₆H₄CO₂Et Cl H 216 NHCH₂C₆H₄CO₂H Cl H 217 NHCOCH₂CH₂CO₂Et Cl H218 NHCOCH₂CH₂CO₂H Cl H 219 NHSO₂CH₃ Cl H 220 NHCH₂CH═CHCO₂Et Cl H 221NHCH₂CH═CHCO₂H Cl H 222 CONH₂ Cl H 223 CH₂CONH₂ Cl H 224 OCH₂CONH₂ Cl H225 CN₄H Cl H 226 Cl CO₂Et H 227 Cl CO₂H H 228 Cl CH₂CO₂Et H 229 ClCH₂CO₂H H 230 Cl OCH₂CO₂Et H 231 Cl OCH₂CO₂H H 232 Cl OCH₂CH₂CH₂PO(OEt)₂H 233 Cl OCH₂CH₂CH₂PO(OH)₂ H 234 Cl OCH₂C₆H₄CO₂Et H 235 Cl OCH₂C₆H₄CO₂HH 236 Cl NHCH₂CO₂Et H 237 Cl NHCH₂CO₂H H 238 Cl NHCH₂CH₂CH₂PO(OEt)₂ H239 Cl NHCH₂CH₂CH₂PO(OH)₂ H 240 Cl NHCH₂C₆H₄CO₂Et H 241 Cl NHCH₂C₆H₄CO₂HH 242 Cl NHCOCH₂CH₂CO₂Et H 243 Cl NHCOCH₂CH₂CO₂H H 244 Cl NHSO₂CH₃ H 245Cl NHCH₂CH═CHCO₂Et H 246 Cl NHCH₂CH═CHCO₂H H 247 Cl CONH₂ H 248 ClCH₂CONH₂ H 249 Cl OCH₂CONH₂ H 250 Cl CN₄H H 251 CO₂Et Cl Cl 252 CO₂H ClCl 253 CH₂CO₂Et Cl Cl 254 CH₂CO₂H Cl Cl 255 OCH₂CO₂Et Cl Cl 256 OCH₂CO₂HCl Cl 257 OCH₂CH₂CH₂PO(OEt)₂ Cl Cl 258 OCH₂CH₂CH₂PO(OH)₂ Cl Cl 259OCH₂C₆H₄CO₂Et Cl Cl 260 OCH₂C₆H₄CO₂H Cl Cl 261 NHCH₂CO₂Et Cl Cl 262NHCH₂CO₂H Cl Cl 263 NHCH₂CH₂CH₂PO(OEt)₂ Cl Cl 264 NHCH₂CH₂CH₂PO(OH)₂ ClCl 265 NHCH₂C₆H₄CO₂Et Cl Cl 266 NHCH₂C₆H₄CO₂H Cl Cl 267 NHCOCH₂CH₂CO₂EtCl Cl 268 NHCOCH₂CH₂CO₂H Cl Cl 269 NHSO₂CH₃ Cl Cl 270 NHCH₂CH═CHCO₂Et ClCl 271 NHCH₂CH═CHCO₂H Cl Cl 272 CONH₂ Cl Cl 273 CH₂CONH₂ Cl Cl 274OCH₂CONH₂ Cl Cl 275 CN₄H Cl Cl 276 Cl CO₂Et Cl 277 Cl CO₂H Cl 278 ClCH₂CO₂Et Cl 279 Cl CH₂CO₂H Cl 280 Cl OCH₂CO₂Et Cl 281 Cl OCH₂CO₂H Cl 282Cl OCH₂CH₂CH₂PO(OEt)₂ Cl 283 Cl OCH₂CH₂CH₂PO(OH)₂ Cl 284 ClOCH₂C₆H₄CO₂Et Cl 285 Cl OCH₂C₆H₄CO₂H Cl 286 Cl NHCH₂CO₂Et Cl 287 ClNHCH₂CO₂H Cl 288 Cl NHCH₂CH₂CH₂PO(OEt)₂ Cl 289 Cl NHCH₂CH₂CH₂PO(OH)₂ Cl290 Cl NHCH₂C₆H₄CO₂Et Cl 291 Cl NHCH₂C₆H₄CO₂H Cl 292 Cl NHCOCH₂CH₂CO₂EtCl 293 Cl NHCOCH₂CH₂CO₂H Cl 294 Cl NHSO₂CH₃ Cl 295 Cl NHCH₂CH═CHCO₂Et Cl296 Cl NHCH₂CH═CHCO₂H Cl 297 Cl CONH₂ Cl 298 Cl CH₂CONH₂ Cl 299 ClOCH₂CONH₂ Cl 300 Cl CN₄H Cl 301 CO₂Et Cl OCH₃ 302 CO₂H Cl OCH₃ 303CH₂CO₂Et Cl OCH₃ 304 CH₂CO₂H Cl OCH₃ 305 OCH₂CO₂Et Cl OCH₃ 306 OCH₂CO₂HCl OCH₃ 307 OCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 308 OCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 309OCH₂C₆H₄CO₂Et Cl OCH₃ 310 OCH₂C₆H₄CO₂H Cl OCH₃ 311 NHCH₂CO₂Et Cl OCH₃312 NHCH₂CO₂H Cl OCH₃ 313 NHCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 314NHCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 315 NHCH₂C₆H₄CO₂Et Cl OCH₃ 316 NHCH₂C₆H₄CO₂HCl OCH₃ 317 NHCOCH₂CH₂CO₂Et Cl OCH₃ 318 NHCOCH₂CH₂CO₂H Cl OCH₃ 319NHSO₂CH₃ Cl OCH₃ 320 NHCH₂CH═CHCO₂Et Cl OCH₃ 321 NHCH₂CH═CHCO₂H Cl OCH₃322 CONH₂ Cl OCH₃ 323 CH₂CONH₂ Cl OCH₃ 324 OCH₂CONH₂ Cl OCH₃ 325 CN₄H ClOCH₃ 326 Cl CO₂Et OCH₃ 327 Cl CO₂H OCH₃ 328 Cl CH₂CO₂Et OCH₃ 329 ClCH₂CO₂H OCH₃ 330 Cl OCH₂CO₂Et OCH₃ 331 Cl OCH₂CO₂H OCH₃ 332 ClOCH₂CH₂CH₂PO(OEt)₂ OCH₃ 333 Cl OCH₂CH₂CH₂PO(OH)₂ OCH₃ 334 ClOCH₂C₆H₄CO₂Et OCH₃ 335 Cl OCH₂C₆H₄CO₂H OCH₃ 336 Cl NHCH₂CO₂Et OCH₃ 337Cl NHCH₂CO₂H OCH₃ 338 Cl NHCH₂CH₂CH₂PO(OEt)₂ OCH₃ 339 ClNHCH₂CH₂CH₂PO(OH)₂ OCH₃ 340 Cl NHCH₂C₆H₄CO₂Et OCH₃ 341 Cl NHCH₂C₆H₄CO₂HOCH₃ 342 Cl NHCOCH₂CH₂CO₂Et OCH₃ 343 Cl NHCOCH₂CH₂CO₂H OCH₃ 344 ClNHSO₂CH₃ OCH₃ 345 Cl NHCH₂CH═CHCO₂Et OCH₃ 346 Cl NHCH₂CH═CHCO₂H OCH₃ 347Cl CONH₂ OCH₃ 348 Cl CH₂CONH₂ OCH₃ 349 Cl OCH₂CONH₂ OCH₃ 350 Cl CN₄HOCH₃ 351 CO₂Et Cl CH₃ 352 CO₂H Cl CH₃ 353 CH₂CO₂Et Cl CH₃ 354 CH₂CO₂H ClCH₃ 355 OCH₂CO₂Et Cl CH₃ 356 OCH₂CO₂H Cl CH₃ 357 OCH₂CH₂CH₂PO(OEt)₂ ClCH₃ 358 OCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 359 OCH₂C₆H₄CO₂Et Cl CH₃ 360OCH₂C₆H₄CO₂H Cl CH₃ 361 NHCH₂CO₂Et Cl CH₃ 362 NHCH₂CO₂H Cl CH₃ 363NHCH₂CH₂CH₂PO(OEt)₂ Cl CH₃ 364 NHCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 365NHCH₂C₆H₄CO₂Et Cl CH₃ 366 NHCH₂C₆H₄CO₂H Cl CH₃ 367 NHCOCH₂CH₂CO₂Et ClCH₃ 368 NHCOCH₂CH₂CO₂H Cl CH₃ 369 NHSO₂CH₃ Cl CH₃ 370 NHCH₂CH═CHCO₂Et ClCH₃ 371 NHCH₂CH═CHCO₂H Cl CH₃ 372 CONH₂ Cl CH₃ 373 CH₂CONH₂ Cl CH₃ 374OCH₂CONH₂ Cl CH₃ 375 CN₄H Cl CH₃ 376 Cl CO₂Et CH₃ 377 Cl CO₂H CH₃ 378 ClCH₂CO₂Et CH₃ 379 Cl CH₂CO₂H CH₃ 380 Cl OCH₂CO₂Et CH₃ 381 Cl OCH₂CO₂H CH₃382 Cl OCH₂CH₂CH₂PO(OEt)₂ CH₃ 383 Cl OCH₂CH₂CH₂PO(OH)₂ CH₃ 384 ClOCH₂C₆H₄CO₂Et CH₃ 385 Cl OCH₂C₆H₄CO₂H CH₃ 386 Cl NHCH₂CO₂Et CH₃ 387 ClNHCH₂CO₂H CH₃ 388 Cl NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 389 Cl NHCH₂CH₂CH₂PO(OH)₂CH₃ 390 Cl NHCH₂C₆H₄CO₂Et CH₃ 391 Cl NHCH₂C₆H₄CO₂H CH₃ 392 ClNHCOCH₂CH₂CO₂Et CH₃ 393 Cl NHCOCH₂CH₂CO₂H CH₃ 394 Cl NHSO₂CH₃ CH₃ 395 ClNHCH₂CH═CHCO₂Et CH₃ 396 Cl NHCH₂CH═CHCO₂H CH₃ 397 Cl CONH₂ CH₃ 398 ClCH₂CONH₂ CH₃ 399 Cl OCH₂CONH₂ CH₃ 400 Cl CN₄H CH₃

TABLE 3b

Ex. # X′ Y′ X 1 CO₂Et H H 2 CO₂H H H 3 CH₂CO₂Et H H 4 CH₂CO₂H H H 5OCH₂CO₂Et H H 6 OCH₂CO₂H H H 7 OCH₂CH₂CH₂PO(OEt)₂ H H 8OCH₂CH₂CH₂PO(OH)₂ H H 9 OCH₂C₆H₄CO₂Et H H 10 OCH₂C₆H₄CO₂H H H 11NHCH₂CO₂Et H H 12 NHCH₂CO₂H H H 13 NHCH₂CH₂CH₂PO(OEt)₂ H H 14NHCH₂CH₂CH₂PO(OH)₂ H H 15 NHCH₂C₆H₄CO₂Et H H 16 NHCH₂C₆H₄CO₂H H H 17NHCOCH₂CH₂CO₂Et H H 18 NHCOCH₂CH₂CO₂H H H 19 NHSO₂CH₃ H H 20NHCH₂CH═CHCO₂Et H H 21 NHCH₂CH═CHCO₂H H H 22 CONH₂ H H 23 CH₂CONH₂ H H24 OCH₂CONH₂ H H 25 CN₄H H H 26 H CO₂Et H 27 H CO₂H H 28 H CH₂CO₂Et H 29H CH₂CO₂H H 30 H OCH₂CO₂Et H 31 H OCH₂CO₂H H 32 H OCH₂CH₂CH₂PO(OEt)₂ H33 H OCH₂CH₂CH₂PO(OH)₂ H 34 H OCH₂C₆H₄CO₂Et H 35 H OCH₂C₆H₄CO₂H H 36 HNHCH₂CO₂Et H 37 H NHCH₂CO₂H H 38 H NHCH₂CH₂CH₂PO(OEt)₂ H 39 HNHCH₂CH₂CH₂PO(OH)₂ H 40 H NHCH₂C₆H₄CO₂Et H 41 H NHCH₂C₆H₄CO₂H H 42 HNHCOCH₂CH₂CO₂Et H 43 H NHCOCH₂CH₂CO₂H H 44 H NHSO₂CH₃ H 45 HNHCH₂CH═CHCO₂Et H 46 H NHCH₂CH═CHCO₂H H 47 H CONH₂ H 48 H CH₂CONH₂ H 49H OCH₂CONH₂ H 50 H CN₄H H 51 CO₂Et H Cl 52 CO₂H H Cl 53 CH₂CO₂Et H Cl 54CH₂CO₂H H Cl 55 OCH₂CO₂Et H Cl 56 OCH₂CO₂H H Cl 57 OCH₂CH₂CH₂PO(OEt)₂ HCl 58 OCH₂CH₂CH₂PO(OH)₂ H Cl 59 OCH₂C₆H₄CO₂Et H Cl 60 OCH₂C₆H₄CO₂H H Cl61 NHCH₂CO₂Et H Cl 62 NHCH₂CO₂H H Cl 63 NHCH₂CH₂CH₂PO(OEt)₂ H Cl 64NHCH₂CH₂CH₂PO(OH)₂ H Cl 65 NHCH₂C₆H₄CO₂Et H Cl 66 NHCH₂C₆H₄CO₂H H Cl 67NHCOCH₂CH₂CO₂Et H Cl 68 NHCOCH₂CH₂CO₂H H Cl 69 NHSO₂CH₃ H Cl 70NHCH₂CH═CHCO₂Et H Cl 71 NHCH₂CH═CHCO₂H H Cl 72 CONH₂ H Cl 73 CH₂CONH₂ HCl 74 OCH₂CONH₂ H Cl 75 CN₄H H Cl 76 H CO₂Et Cl 77 H CO₂H Cl 78 HCH₂CO₂Et Cl 79 H CH₂CO₂H Cl 80 H OCH₂CO₂Et Cl 81 H OCH₂CO₂H Cl 82 HOCH₂CH₂CH₂PO(OEt)₂ Cl 83 H OCH₂CH₂CH₂PO(OH)₂ Cl 84 H OCH₂C₆H₄CO₂Et Cl 85H OCH₂C₆H₄CO₂H Cl 86 H NHCH₂CO₂Et Cl 87 H NHCH₂CO₂H Cl 88 HNHCH₂CH₂CH₂PO(OEt)₂ Cl 89 H NHCH₂CH₂CH₂PO(OH)₂ Cl 90 H NHCH₂C₆H₄CO₂Et Cl91 H NHCH₂C₆H₄CO₂H Cl 92 H NHCOCH₂CH₂CO₂Et Cl 93 H NHCOCH₂CH₂CO₂H Cl 94H NHSO₂CH₃ Cl 95 H NHCH₂CH═CHCO₂Et Cl 96 H NHCH₂CH═CHCO₂H Cl 97 H CONH₂Cl 98 H CH₂CONH₂ Cl 99 H OCH₂CONH₂ Cl 100 H CN₄H Cl 101 CO₂Et H OCH₃ 102CO₂H H OCH₃ 103 CH₂CO₂Et H OCH₃ 104 CH₂CO₂H H OCH₃ 105 OCH₂CO₂Et H OCH₃106 OCH₂CO₂H H OCH₃ 107 OCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 108 OCH₂CH₂CH₂PO(OH)₂H OCH₃ 109 OCH₂C₆H₄CO₂Et H OCH₃ 110 OCH₂C₆H₄CO₂H H OCH₃ 111 NHCH₂CO₂Et HOCH₃ 112 NHCH₂CO₂H H OCH₃ 113 NHCH₂CH₂CH₂PO(OEt)₂ H OCH₃ 114NHCH₂CH₂CH₂PO(OH)₂ H OCH₃ 115 NHCH₂C₆H₄CO₂Et H OCH₃ 116 NHCH₂C₆H₄CO₂H HOCH₃ 117 NHCOCH₂CH₂CO₂Et H OCH₃ 118 NHCOCH₂CH₂CO₂H H OCH₃ 119 NHSO₂CH₃ HOCH₃ 120 NHCH₂CH═CHCO₂Et H OCH₃ 121 NHCH₂CH═CHCO₂H H OCH₃ 122 CONH₂ HOCH₃ 123 CH₂CONH₂ H OCH₃ 124 OCH₂CONH₂ H OCH₃ 125 CN₄H H OCH₃ 126 HCO₂Et OCH₃ 127 H CO₂H OCH₃ 128 H CH₂CO₂Et OCH₃ 129 H CH₂CO₂H OCH₃ 130 HOCH₂CO₂Et OCH₃ 131 H OCH₂CO₂H OCH₃ 132 H OCH₂CH₂CH₂PO(OEt)₂ OCH₃ 133 HOCH₂CH₂CH₂PO(OH)₂ OCH₃ 134 H OCH₂C₆H₄CO₂Et OCH₃ 135 H OCH₂C₆H₄CO₂H OCH₃136 H NHCH₂CO₂Et OCH₃ 137 H NHCH₂CO₂H OCH₃ 138 H NHCH₂CH₂CH₂PO(OEt)₂OCH₃ 139 H NHCH₂CH₂CH₂PO(OH)₂ OCH₃ 140 H NHCH₂C₆H₄CO₂Et OCH₃ 141 HNHCH₂C₆H₄CO₂H OCH₃ 142 H NHCOCH₂CH₂CO₂Et OCH₃ 143 H NHCOCH₂CH₂CO₂H OCH₃144 H NHSO₂CH₃ OCH₃ 145 H NHCH₂CH═CHCO₂Et OCH₃ 146 H NHCH₂CH═CHCO₂H OCH₃147 H CONH₂ OCH₃ 148 H CH₂CONH₂ OCH₃ 149 H OCH₂CONH₂ OCH₃ 150 H CN₄HOCH₃ 151 CO₂Et H CH₃ 152 CO₂H H CH₃ 153 CH₂CO₂Et H CH₃ 154 CH₂CO₂H H CH₃155 OCH₂CO₂Et H CH₃ 156 OCH₂CO₂H H CH₃ 157 OCH₂CH₂CH₂PO(OEt)₂ H CH₃ 158OCH₂CH₂CH₂PO(OH)₂ H CH₃ 159 OCH₂C₆H₄CO₂Et H CH₃ 160 OCH₂C₆H₄CO₂H H CH₃161 NHCH₂CO₂Et H CH₃ 162 NHCH₂CO₂H H CH₃ 163 NHCH₂CH₂CH₂PO(OEt)₂ H CH₃164 NHCH₂CH₂CH₂PO(OH)₂ H CH₃ 165 NHCH₂C₆H₄CO₂Et H CH₃ 166 NHCH₂C₆H₄CO₂HH CH₃ 167 NHCOCH₂CH₂CO₂Et H CH₃ 168 NHCOCH₂CH₂CO₂H H CH₃ 169 NHSO₂CH₃ HCH₃ 170 NHCH₂CH═CHCO₂Et H CH₃ 171 NHCH₂CH═CHCO₂H H CH₃ 172 CONH₂ H CH₃173 CH₂CONH₂ H CH₃ 174 OCH₂CONH₂ H CH₃ 175 CN₄H H CH₃ 176 H CO₂Et CH₃177 H CO₂H CH₃ 178 H CH₂CO₂Et CH₃ 179 H CH₂CO₂H CH₃ 180 H OCH₂CO₂Et CH₃181 H OCH₂CO₂H CH₃ 182 H OCH₂CH₂CH₂PO(OEt)₂ CH₃ 183 H OCH₂CH₂CH₂PO(OH)₂CH₃ 184 H OCH₂C₆H₄CO₂Et CH₃ 185 H OCH₂C₆H₄CO₂H CH₃ 186 H NHCH₂CO₂Et CH₃187 H NHCH₂CO₂H CH₃ 188 H NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 189 HNHCH₂CH₂CH₂PO(OH)₂ CH₃ 190 H NHCH₂C₆H₄CO₂Et CH₃ 191 H NHCH₂C₆H₄CO₂H CH₃192 H NHCOCH₂CH₂CO₂Et CH₃ 193 H NHCOCH₂CH₂CO₂H CH₃ 194 H NHSO₂CH₃ CH₃195 H NHCH₂CH═CHCO₂Et CH₃ 196 H NHCH₂CH═CHCO₂H CH₃ 197 H CONH₂ CH₃ 198 HCH₂CONH₂ CH₃ 199 H OCH₂CONH₂ CH₃ 200 H CN₄H CH₃ 201 CO₂Et Cl H 202 CO₂HCl H 203 CH₂CO₂Et Cl H 204 CH₂CO₂H Cl H 205 OCH₂CO₂Et Cl H 206 OCH₂CO₂HCl H 207 OCH₂CH₂CH₂PO(OEt)₂ Cl H 208 OCH₂CH₂CH₂PO(OH)₂ Cl H 209OCH₂C₆H₄CO₂Et Cl H 210 OCH₂C₆H₄CO₂H Cl H 211 NHCH₂CO₂Et Cl H 212NHCH₂CO₂H Cl H 213 NHCH₂CH₂CH₂PO(OEt)₂ Cl H 214 NHCH₂CH₂CH₂PO(OH)₂ Cl H215 NHCH₂C₆H₄CO₂Et Cl H 216 NHCH₂C₆H₄CO₂H Cl H 217 NHCOCH₂CH₂CO₂Et Cl H218 NHCOCH₂CH₂CO₂H Cl H 219 NHSO₂CH₃ Cl H 220 NHCH₂CH═CHCO₂Et Cl H 221NHCH₂CH═CHCO₂H Cl H 222 CONH₂ Cl H 223 CH₂CONH₂ Cl H 224 OCH₂CONH₂ Cl H225 CN₄H Cl H 226 Cl CO₂Et H 227 Cl CO₂H H 228 Cl CH₂CO₂Et H 229 ClCH₂CO₂H H 230 Cl OCH₂CO₂Et H 231 Cl OCH₂CO₂H H 232 Cl OCH₂CH₂CH₂PO(OEt)₂H 233 Cl OCH₂CH₂CH₂PO(OH)₂ H 234 Cl OCH₂C₆H₄CO₂Et H 235 Cl OCH₂C₆H₄CO₂HH 236 Cl NHCH₂CO₂Et H 237 Cl NHCH₂CO₂H H 238 Cl NHCH₂CH₂CH₂PO(OEt)₂ H239 Cl NHCH₂CH₂CH₂PO(OH)₂ H 240 Cl NHCH₂C₆H₄CO₂Et H 241 Cl NHCH₂C₆H₄CO₂HH 242 Cl NHCOCH₂CH₂CO₂Et H 243 Cl NHCOCH₂CH₂CO₂H H 244 Cl NHSO₂CH₃ H 245Cl NHCH₂CH═CHCO₂Et H 246 Cl NHCH₂CH═CHCO₂H H 247 Cl CONH₂ H 248 ClCH₂CONH₂ H 249 Cl OCH₂CONH₂ H 250 Cl CN₄H H 251 CO₂Et Cl Cl 252 CO₂H ClCl 253 CH₂CO₂Et Cl Cl 254 CH₂CO₂H Cl Cl 255 OCH₂CO₂Et Cl Cl 256 OCH₂CO₂HCl Cl 257 OCH₂CH₂CH₂PO(OEt)₂ Cl Cl 258 OCH₂CH₂CH₂PO(OH)₂ Cl Cl 259OCH₂C₆H₄CO₂Et Cl Cl 260 OCH₂C₆H₄CO₂H Cl Cl 261 NHCH₂CO₂Et Cl Cl 262NHCH₂CO₂H Cl Cl 263 NHCH₂CH₂CH₂PO(OEt)₂ Cl Cl 264 NHCH₂CH₂CH₂PO(OH)₂ ClCl 265 NHCH₂C₆H₄CO₂Et Cl Cl 266 NHCH₂C₆H₄CO₂H Cl Cl 267 NHCOCH₂CH₂CO₂EtCl Cl 268 NHCOCH₂CH₂CO₂H Cl Cl 269 NHSO₂CH₃ Cl Cl 270 NHCH₂CH═CHCO₂Et ClCl 271 NHCH₂CH═CHCO₂H Cl Cl 272 CONH₂ Cl Cl 273 CH₂CONH₂ Cl Cl 274OCH₂CONH₂ Cl Cl 275 CN₄H Cl Cl 276 Cl CO₂Et Cl 277 Cl CO₂H Cl 278 ClCH₂CO₂Et Cl 279 Cl CH₂CO₂H Cl 280 Cl OCH₂CO₂Et Cl 281 Cl OCH₂CO₂H Cl 282Cl OCH₂CH₂CH₂PO(OEt)₂ Cl 283 Cl OCH₂CH₂CH₂PO(OH)₂ Cl 284 ClOCH₂C₆H₄CO₂Et Cl 285 Cl OCH₂C₆H₄CO₂H Cl 286 Cl NHCH₂CO₂Et Cl 287 ClNHCH₂CO₂H Cl 288 Cl NHCH₂CH₂CH₂PO(OEt)₂ Cl 289 Cl NHCH₂CH₂CH₂PO(OH)₂ Cl290 Cl NHCH₂C₆H₄CO₂Et Cl 291 Cl NHCH₂C₆H₄CO₂H Cl 292 Cl NHCOCH₂CH₂CO₂EtCl 293 Cl NHCOCH₂CH₂CO₂H Cl 294 Cl NHSO₂CH₃ Cl 295 Cl NHCH₂CH═CHCO₂Et Cl296 Cl NHCH₂CH═CHCO₂H Cl 297 Cl CONH₂ Cl 298 Cl CH₂CONH₂ Cl 299 ClOCH₂CONH₂ Cl 300 Cl CN₄H Cl 301 CO₂Et Cl OCH₃ 302 CO₂H Cl OCH₃ 303CH₂CO₂Et Cl OCH₃ 304 CH₂CO₂H Cl OCH₃ 305 OCH₂CO₂Et Cl OCH₃ 306 OCH₂CO₂HCl OCH₃ 307 OCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 308 OCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 309OCH₂C₆H₄CO₂Et Cl OCH₃ 310 OCH₂C₆H₄CO₂H Cl OCH₃ 311 NHCH₂CO₂Et Cl OCH₃312 NHCH₂CO₂H Cl OCH₃ 313 NHCH₂CH₂CH₂PO(OEt)₂ Cl OCH₃ 314NHCH₂CH₂CH₂PO(OH)₂ Cl OCH₃ 315 NHCH₂C₆H₄CO₂Et Cl OCH₃ 316 NHCH₂C₆H₄CO₂HCl OCH₃ 317 NHCOCH₂CH₂CO₂Et Cl OCH₃ 318 NHCOCH₂CH₂CO₂H Cl OCH₃ 319NHSO₂CH₃ Cl OCH₃ 320 NHCH₂CH═CHCO₂Et Cl OCH₃ 321 NHCH₂CH═CHCO₂H Cl OCH₃322 CONH₂ Cl OCH₃ 323 CH₂CONH₂ Cl OCH₃ 324 OCH₂CONH₂ Cl OCH₃ 325 CN₄H ClOCH₃ 326 Cl CO₂Et OCH₃ 327 Cl CO₂H OCH₃ 328 Cl CH₂CO₂Et OCH₃ 329 ClCH₂CO₂H OCH₃ 330 Cl OCH₂CO₂Et OCH₃ 331 Cl OCH₂CO₂H OCH₃ 332 ClOCH₂CH₂CH₂PO(OEt)₂ OCH₃ 333 Cl OCH₂CH₂CH₂PO(OH)₂ OCH₃ 334 ClOCH₂C₆H₄CO₂Et OCH₃ 335 Cl OCH₂C₆H₄CO₂H OCH₃ 336 Cl NHCH₂CO₂Et OCH₃ 337Cl NHCH₂CO₂H OCH₃ 338 Cl NHCH₂CH₂CH₂PO(OEt)₂ OCH₃ 339 ClNHCH₂CH₂CH₂PO(OH)₂ OCH₃ 340 Cl NHCH₂C₆H₄CO₂Et OCH₃ 341 Cl NHCH₂C₆H₄CO₂HOCH₃ 342 Cl NHCOCH₂CH₂CO₂Et OCH₃ 343 Cl NHCOCH₂CH₂CO₂H OCH₃ 344 ClNHSO₂CH₃ OCH₃ 345 Cl NHCH₂CH═CHCO₂Et OCH₃ 346 Cl NHCH₂CH═CHCO₂H OCH₃ 347Cl CONH₂ OCH₃ 348 Cl CH₂CONH₂ OCH₃ 349 Cl OCH₂CONH₂ OCH₃ 350 Cl CN₄HOCH₃ 351 CO₂Et Cl CH₃ 352 CO₂H Cl CH₃ 353 CH₂CO₂Et Cl CH₃ 354 CH₂CO₂H ClCH₃ 355 OCH₂CO₂Et Cl CH₃ 356 OCH₂CO₂H Cl CH₃ 357 OCH₂CH₂CH₂PO(OEt)₂ ClCH₃ 358 OCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 359 OCH₂C₆H₄CO₂Et Cl CH₃ 360OCH₂C₆H₄CO₂H Cl CH₃ 361 NHCH₂CO₂Et Cl CH₃ 362 NHCH₂CO₂H Cl CH₃ 363NHCH₂CH₂CH₂PO(OEt)₂ Cl CH₃ 364 NHCH₂CH₂CH₂PO(OH)₂ Cl CH₃ 365NHCH₂C₆H₄CO₂Et Cl CH₃ 366 NHCH₂C₆H₄CO₂H Cl CH₃ 367 NHCOCH₂CH₂CO₂Et ClCH₃ 368 NHCOCH₂CH₂CO₂H Cl CH₃ 369 NHSO₂CH₃ Cl CH₃ 370 NHCH₂CH═CHCO₂Et ClCH₃ 371 NHCH₂CH═CHCO₂H Cl CH₃ 372 CONH₂ Cl CH₃ 373 CH₂CONH₂ Cl CH₃ 374OCH₂CONH₂ Cl CH₃ 375 CN₄H Cl CH₃ 376 Cl CO₂Et CH₃ 377 Cl CO₂H CH₃ 378 ClCH₂CO₂Et CH₃ 379 Cl CH₂CO₂H CH₃ 380 Cl OCH₂CO₂Et CH₃ 381 Cl OCH₂CO₂H CH₃382 Cl OCH₂CH₂CH₂PO(OEt)₂ CH₃ 383 Cl OCH₂CH₂CH₂PO(OH)₂ CH₃ 384 ClOCH₂C₆H₄CO₂Et CH₃ 385 Cl OCH₂C₆H₄CO₂H CH₃ 386 Cl NHCH₂CO₂Et CH₃ 387 ClNHCH₂CO₂H CH₃ 388 Cl NHCH₂CH₂CH₂PO(OEt)₂ CH₃ 389 Cl NHCH₂CH₂CH₂PO(OH)₂CH₃ 390 Cl NHCH₂C₆H₄CO₂Et CH₃ 391 Cl NHCH₂C₆H₄CO₂H CH₃ 392 ClNHCOCH₂CH₂CO₂Et CH₃ 393 Cl NHCOCH₂CH₂CO₂H CH₃ 394 Cl NHSO₂CH₃ CH₃ 395 ClNHCH₂CH═CHCO₂Et CH₃ 396 Cl NHCH₂CH═CHCO₂H CH₃ 397 Cl CONH₂ CH₃ 398 ClCH₂CONH₂ CH₃ 399 Cl OCH₂CONH₂ CH₃ 400 Cl CN₄H CH₃

TABLE 4

Ex. # Y V O n 1 Cl CO₂Et N 1 2 Cl CO₂H N 1 3 Cl CONH₂ N 1 4 Cl CN₄H N 15 CH₃ CO₂Et N 1 6 CH₃ CO₂H N 1 7 CH₃ CONH₂ N 1 8 CH₃ CN₄H N 1 9 OCH₃CO₂Et N 1 10 OCH₃ CO₂H N 1 11 OCH₃ CONH₂ N 1 12 OCH₃ CN₄H N 1 13CH(CH₃)₂ CO₂Et N 1 14 CH(CH₃)₂ CO₂H N 1 15 CH(CH₃)₂ CONH₂ N 1 16CH(CH₃)₂ CN₄H N 1 17 Cl CO₂Et N 2 18 Cl CO₂H N 2 19 Cl CONH₂ N 2 20 ClCN₄H N 2 21 CH₃ CO₂Et N 2 22 CH₃ CO₂H N 2 23 CH₃ CONH₂ N 2 24 CH₃ CN₄H N2 25 OCH₃ CO₂Et N 2 26 OCH₃ CO₂H N 2 27 OCH₃ CONH₂ N 2 28 OCH₃ CN₄H N 229 CH(CH₃)₂ CO₂Et N 2 30 CH(CH₃)₂ CO₂H N 2 31 CH(CH₃)₂ CONH₂ N 2 32CH(CH₃)₂ CN₄H N 2 33 Cl CO₂Et CH 1 34 Cl CO₂H CH 1 35 Cl CONH₂ CH 1 36Cl CN₄H CH 1 37 CH₃ CO2Et CH 1 38 CH₃ CO₂H CH 1 39 CH₃ CONH₂ CH 1 40 CH₃CN₄H CH 1 41 OCH₃ CO₂Et CH 1 42 OCH₃ CO₂H CH 1 43 OCH₃ CONH₂ CH 1 44OCH₃ CN₄H CH 1 45 CH(CH₃)₂ CO₂Et CH 1 46 CH(CH₃)₂ CO₂H CH 1 47 CH(CH₃)₂CONH₂ CH 1 48 CH(CH₃)₂ CN₄H CH 1 49 Cl CO₂Et CH 2 50 Cl CO₂H CH 2 51 ClCONH₂ CH 2 52 Cl CN₄H CH 2 53 CH₃ CO₂Et CH 2 54 CH₃ CO₂H CH 2 55 CH₃CONH₂ CH 2 56 CH₃ CN₄H CH 2 57 OCH₃ CO₂Et CH 2 58 OCH₃ CO₂H CH 2 59 OCH₃CONH₂ CH 2 60 OCH₃ CN₄H CH 2 61 CH(CH₃)₂ CO₂Et CH 2 62 CH(CH₃)₂ CO₂H CH2 63 CH(CH₃)₂ CONH₂ CH 2 64 CH(CH₃)₂ CN₄H CH 
 2.


10. A pharmaceutical composition, comprising: a compound according toclaim 1 and a pharmaceutically acceptable carrier.
 11. A compound ofclaim 1, wherein the compound is:

or a pharmaceutically acceptable salt thereof.
 12. A compound of claim1, wherein the compound is:

or a pharmaceutically acceptable salt thereof.
 13. A compound of claim1, wherein the compound is:

or a pharmaceutically acceptable salt thereof.
 14. A compound of claim1, wherein the compound is:

or a pharmaceutically acceptable salt thereof.
 15. A compound of claim1, wherein the compound is:

or a pharmaceutically acceptable salt thereof.
 16. A compound of claim1, wherein the compound is:

or a pharmaceutically acceptable salt thereof.
 17. A compound of claim1, wherein the compound is:

or a pharmaceutically acceptable salt thereof.
 18. A pharmaceuticalcomposition, comprising: a compound according to claim 2 and apharmaceutically acceptable carrier.
 19. A pharmaceutical composition,comprising: a compound according to claim 3 and a pharmaceuticallyacceptable carrier.
 20. A pharmaceutical composition, comprising: acompound according to claim 4 and a pharmaceutically acceptable carrier.21. A pharmaceutical composition, comprising: a compound according toclaim 5 and a pharmaceutically acceptable carrier.
 22. A pharmaceuticalcomposition, comprising: a compound according to claim 6 and apharmaceutically acceptable carrier.
 23. A pharmaceutical composition,comprising: a compound according to claim 7 and a pharmaceuticallyacceptable carrier.
 24. A pharmaceutical composition, comprising: acompound according to claim 8 and a pharmaceutically acceptable carrier.25. A pharmaceutical composition, comprising: a compound according toclaim 9 and a pharmaceutically acceptable carrier.
 26. A pharmaceuticalcomposition, comprising: a compound according to claim 11 and apharmaceutically acceptable carrier.
 27. A pharmaceutical composition,comprising: a compound according to claim 12 and a pharmaceuticallyacceptable carrier.
 28. A pharmaceutical composition, comprising: acompound according to claim 13 and a pharmaceutically acceptablecarrier.
 29. A pharmaceutical composition, comprising: a compoundaccording to claim 14 and a pharmaceutically acceptable carrier.
 30. Apharmaceutical composition, comprising: a compound according to claim 15and a pharmaceutically acceptable carrier.
 31. A pharmaceuticalcomposition, comprising: a compound according to claim 16 and apharmaceutically acceptable carrier.
 32. A pharmaceutical composition,comprising: a compound according to claim 17 and a pharmaceuticallyacceptable carrier.